|
Abacavir
(Archary 2019)
|
Two-compartment population PK model for abacavir in severely
malnourished HIV-infected children (Archary 2019); CL/F steps up between
day 1 and day 14 of antiretroviral treatment and bioavailability is 31%
higher in the early-ART arm
|
|
Abacavir
(Tikiso 2021)
|
Two-compartment population PK model for oral abacavir in HIV-infected
African children (Tikiso 2021), with a Savic 2007-style analytical
transit-compartment chain feeding a first-order absorption depot,
allometric body-weight scaling on disposition (0.75 on CL/Q, 1 on Vc/Vp
at 70 kg), sigmoidal Hill-type maturation of CL on postmenstrual age,
and multiplicative covariate effects of efavirenz co-medication on CL,
rifampicin + super-boosted lopinavir/ritonavir co-medication on F,
fixed-dose-combination tablet formulation on MTT, and a time-decaying
malnutrition effect on F and CL.
|
|
Abatacept
(Gandhi 2021)
|
Two-compartment population PK model for abatacept (CTLA4-Ig Fc-fusion)
pooled across adults with rheumatoid arthritis and patients aged 2-17
years with polyarticular juvenile idiopathic arthritis (Gandhi 2021),
with first-order SC absorption, zero-order IV infusion support,
first-order linear elimination, logit-scale SC bioavailability with
disease/age/weight covariates, and a KA parameterisation that enforces
KA > k_el.
|
|
Abatacept
(Li 2019)
|
Two-compartment population PK model for abatacept (CTLA4-Ig Fc-fusion)
in adults with rheumatoid arthritis (Li 2019), with first-order SC
absorption, zero-order IV infusion support, first-order linear
elimination, logit-scale SC bioavailability, full-block IIV on
CL/VC/Q/VP, and a KA parameterisation that enforces KA > k_el.
|
|
Abatacept
(Lon 2013)
|
Two-compartment population PK model with linear elimination and
short-term zero-order SC absorption for abatacept (CTLA-4Ig Fc-fusion)
in male Lewis rats with collagen-induced arthritis (Lon 2013).
|
|
Abatacept
(Takahashi 2023)
|
Two-compartment IV population PK model for abatacept (CTLA4-Ig
Fc-fusion) pooled across 685 adult/pediatric patients with rheumatoid
arthritis or polyarticular juvenile idiopathic arthritis and
adult/pediatric patients receiving allogeneic hematopoietic cell
transplantation in the ABA2 trial (Takahashi 2023). Linear elimination,
allometric weight scaling on CL/Vc/Vp/Q with estimated exponents, and a
three-level cohort categorical (RA/JIA reference, ABA2 HLA 7/8, ABA2 HLA
8/8) on CL and Vc.
|
|
Abatacept
(Zhong 2026)
|
Two-compartment population PK model for abatacept (CTLA4-Ig Fc-fusion)
pooled across 9 phase 2/3 studies (Zhong 2026): adults with rheumatoid
arthritis, patients aged 2-17 years with polyarticular juvenile
idiopathic arthritis, and patients aged 6+ years with hematologic
malignancies receiving HLA-matched unrelated-donor HSCT (the ABA2
trial). Final model has zero-order IV infusion, first-order SC
absorption, first-order linear elimination, additive plus proportional
residual error, allometric weight on CL/VC/VP, hepatic (AST) and renal
(cGFR) markers on CL, sex on CL and VC, two HSCT cohort indicators
(7-of-8 and 8-of-8 HLA-matched URD) on CL/VC, and a logit-scale SC
bioavailability sub-model with weight, age, and pJIA-disease covariates
fixed to a previously developed internal JIA PPK model (values match
Gandhi 2021).
|
|
Acetaminophen
(vanRongen 2016)
|
Parent-and-metabolites population PK model for intravenous acetaminophen
(paracetamol) and its glucuronide, sulphate, and CYP2E1-oxidation
(cysteine + mercapturate) metabolites in morbidly obese and non-obese
adults (van Rongen 2016). One-compartment plasma disposition for parent
acetaminophen with four parallel elimination pathways from the central
compartment (glucuronidation, sulphation, CYP2E1 oxidation, and
unchanged renal); one-compartment plasma disposition for glucuronide and
cysteine + mercapturate metabolites each fed via a
single-transit-compartment delay; two-compartment plasma disposition for
sulphate (central + peripheral, fixed equal volumes 5.66 L each). Lean
body weight (LBW; Janmahasatian et al. 2005 equation) enters as a
power-law covariate on parent V, all three formation clearances, the
CYP2E1 transit rate constant, and glucuronide elimination CL. Total body
weight enters on the glucuronide volume of distribution.
|
|
Adalimumab
(Drweesh 2026)
|
One-compartment population PK model with first-order subcutaneous
absorption and linear elimination for adalimumab originator (Humira) and
biosimilars (Amgevita, Hyrimoz) in adults with inflammatory bowel
disease and other autoimmune disorders, fit to multicenter
therapeutic-drug-monitoring trough data from Saudi Arabia and Qatar
(Drweesh 2026). Structural backbone (V/F, IIV variances, residual error)
inherited from Marquez-Megias 2023 because Drweesh 2026 reports only ka
(fixed) and the typical clearance value.
|
|
Adalimumab
(Marquez-Megias 2023)
|
One-compartment population PK model with first-order subcutaneous
absorption and linear elimination for adalimumab in adults with
inflammatory bowel disease, with albumin and anti-drug-antibody
covariates on apparent clearance (Marquez-Megias 2023)
|
|
Adecatumumab
(Cao 2013)
|
Second-generation minimal physiologically-based PK (mPBPK) model for
adecatumumab in adults (Cao 2013 Model A; clearance from plasma)
|
|
Agomelatine
(Xie 2019)
|
A semiphysiological population pharmacokinetic model of agomelatine and
its metabolites in Chinese healthy volunteers
|
|
Alemtuzumab
(Mould 2007)
|
Two-compartment population PK model with Michaelis-Menten elimination
for alemtuzumab in B-cell chronic lymphocytic leukaemia (Mould 2007)
|
|
Alirocumab
(Martinez 2019)
|
Two-compartment population PK model for alirocumab in healthy volunteers
and adults with hypercholesterolemia (Martinez 2019, Part I), with
first-order SC absorption (with lag time), linear plus Michaelis-Menten
(target-mediated) elimination from the central compartment, and
logit-transformed bioavailability.
|
|
Alvespimycin
(Aregbe 2012)
|
Three-compartment population PK model for the heat shock protein 90
inhibitor 17-DMAG (alvespimycin, NSC 707545) given as a 1 h IV infusion
to adult patients with advanced solid tumors (Aregbe 2012), with
first-order elimination, log-normal IIV on CL/Q3/V1/V2/V3, and
between-occasion variability on Q2 and V1 multiplexed by an OCC
indicator across up to five daily dosing occasions.
|
|
Amatuximab
(Gupta 2016)
|
Two-compartment population PK model with parallel linear and
Michaelis-Menten elimination for amatuximab in patients with advanced
cancers / malignant pleural mesothelioma (Gupta 2016)
|
|
Amifampridine
(Thakkar 2017)
|
Joint parent-metabolite population PK + fractional-Emax PD model for
3,4-diaminopyridine (3,4-DAP, amifampridine) free base and its N-acetyl
metabolite 3-Ac DAP in 49 adults with Lambert-Eaton myasthenia (Thakkar
2017). Two-compartment parent + one-compartment metabolite with Fm fixed
to 1 (all parent clearance forms metabolite). Body weight is
allometrically scaled on CL/F and CLm/F3ACDAP (exponent 0.75 fixed) and
linearly on Vp/F (exponent 1 fixed), all with reference weight 82 kg.
Serum creatinine acts on CLm/F3ACDAP through (0.8/SCR)^0.7 with median
SCR 0.8 mg/dL. The PD submodel describes the Triple Timed Up and Go
(3TUG) score in seconds via a fractional-inhibitory Emax equation Effect
= E0 * (1 - Emax * Cp / (EC50 + Cp)) where Cp is the parent 3,4-DAP
plasma concentration in ng/mL.
|
|
Amikacin
(Delattre 2010)
|
Two-compartment IV population PK model for amikacin in critically ill
adult patients with severe sepsis or septic shock during the first 24
hours of antibiotic treatment (Delattre 2010)
|
|
Amlitelimab
(Tiraboschi 2025)
|
Two-compartment population PK model for amlitelimab (anti-OX40L mAb) in
adults, with parallel first-order and Michaelis-Menten (TMDD)
elimination, SC absorption with lag time, allometric body-weight
scaling, and EASI / albumin covariate effects (Tiraboschi 2025)
|
|
Anifrolumab
(Almquist 2022)
|
Two-compartment QSS-TMDD population PK model for anifrolumab
(anti-IFNAR1 IgG1-kappa) in healthy volunteers and adults with systemic
lupus erythematosus (Almquist 2022): linear plus quasi-steady-state
target-mediated elimination via a dynamic IFNAR1 receptor pool,
time-varying linear clearance (Emax-on-time), and IFNGS-high/low and
body-weight covariate effects.
|
|
Anrukinzumab
(Hua 2015)
|
Two-compartment population PK model for anrukinzumab (anti-IL-13 IgG1
monoclonal antibody) with first-order SC absorption and linear
elimination, pooling healthy volunteers, mild-to-moderate asthma,
moderate-to-severe asthma, and ulcerative colitis patients (Hua 2015)
|
|
Artesunate
(Hendriksen 2013)
|
Joint parent-metabolite population PK model of intramuscular artesunate
(ARS) and its active metabolite dihydroartemisinin (DHA) in 70 African
children aged 7 months to 11 years admitted with severe Plasmodium
falciparum malaria (Hendriksen 2013). Each species has a one-compartment
apparent-volume disposition; ARS is delivered by a zero-order input over
a 1-min fixed duration (the IM absorption from the injection site, fixed
because too few samples were collected during the absorption phase to
identify the rate) and is converted mole-for-mole to DHA with no
separate parent elimination. Body weight is the dominant covariate
(allometric scaling with fixed exponents 0.75 on apparent clearance and
1.0 on apparent volume for both species; reference 10.9 kg), with
hemoglobin additionally lowering DHA clearance by 10.2% per g/dL above
the reference 7.1 g/dL.
|
|
Astegolimab
(Kotani 2022)
|
Two-compartment population PK model for astegolimab (anti-ST2 IgG2) in
adults with severe asthma (Kotani 2022)
|
|
Asundexian
(Yassen 2025)
|
Two-compartment population PK model with two transit absorption
compartments for asundexian, an oral selective Factor XIa inhibitor, in
healthy volunteers and adult patients at risk for thromboembolic /
cardiovascular events (Yassen 2025)
|
|
Avelumab
(Masters 2022)
|
Two-compartment population PK model for avelumab (anti-PD-L1 IgG1) with
time-dependent clearance in patients with advanced solid tumors (Masters
2022)
|
|
Axatilimab
(Yang 2024)
|
Semimechanistic population PK/PD model for axatilimab (anti-CSF-1R IgG4
monoclonal antibody) in healthy adults, patients with advanced solid
tumors, and patients with chronic graft-versus-host disease (Yang 2024).
Two-compartment IV PK with parallel linear clearance and CSF-1R-mediated
saturable elimination via competitive Hill binding with circulating
CSF-1; CSF-1, NCMC, AST, and CPK pharmacodynamics integrated as turnover
indirect-response biomarkers.
|
|
Azithromycin
(Sampson 2014)
|
Four-compartment mamillary population PK model for oral azithromycin
simultaneously describing concentrations in whole blood, peripheral
blood mononuclear cells (PBMCs), and polymorphonuclear cells (PMNs) in
healthy adults (Sampson 2014). First-order absorption with lag;
unidirectional flow from central to PBMC and to PMN compartments;
bidirectional flow between central and a peripheral tissue compartment;
elimination from central, PBMC, and PMN compartments. The observed
whole-blood concentration is a weighted sum of plasma, PBMC, and PMN
concentrations.
|
|
Bapineuzumab
(Hu 2014)
|
Two-compartment population PK model for bapineuzumab in adults with
mild-to-moderate Alzheimer’s disease following IV administration (Hu
2014, reduced model)
|
|
BAY81
8973 (Garmann 2017)
|
Two-compartment population PK model for BAY 81-8973 (Kovaltry,
full-length unmodified recombinant human factor VIII) in patients with
severe haemophilia A aged 1-61 years pooled from the LEOPOLD I, II and
Kids trials (Garmann 2017). Final model uses NONMEM M3 likelihood for
samples below the chromogenic-assay limit of quantitation (1.5 IU/dL).
|
|
Bedaquiline
(Svensson 2018)
|
Three-compartment population PK model for the antimycobacterial
bedaquiline (BDQ) and a two-compartment N-desmethyl metabolite M2 in
healthy adult volunteers following single 400 mg oral doses, with
four-transit-compartment first-order absorption (rate of absorption from
the last transit compartment fixed equal to the inter-transit transfer
rate, i.e. KA = KTR) and a multiplicative formulation effect adding 23%
to the typical mean absorption time when the four 100 mg tablets are
suspended in water before swallowing relative to swallowing the tablets
whole.
|
|
Belantamab
(Papathanasiou 2025)
|
Two-compartment population PK model for the antibody-drug conjugate
(ADC) belantamab mafodotin in patients with relapsed/refractory multiple
myeloma, with sigmoidal time-varying clearance and covariate effects of
baseline body weight, BMI, albumin, soluble BCMA, serum IgG, race, and
combination therapy (Papathanasiou 2025; ADC moiety only – the
cys-mcMMAF payload sub-model is not included; see vignette for
rationale)
|
|
Belatacept
(Shen 2013)
|
PK/PD model for belatacept (CTLA-4/IgG1 fusion protein, selective T-cell
co-stimulation blocker) in adult kidney transplant recipients (Shen
2013). The PK side is a one-compartment IV-infusion model derived from
the paper’s noncompartmental analysis (Table 1, 10 mg/kg substudy, n =
10): typical clearance and volume for a 70 kg adult are set so the model
reproduces the reported geometric-mean CL, Vss, AUC over a 4-week dosing
interval, and ~8-9 day terminal half-life. The PD side is the inhibitory
Emax model of Eq. 2 (Section 3.2, n = 62 in the phase II
corticosteroid-avoidance substudy IM103034) describing free CD86
receptor expression on peripheral-blood monocytes (MESF) as E0 - Emax *
Cc / (EC50 + Cc); CD86 receptor occupancy is derived as 100 * (E0 -
freeCD86) / E0. Belatacept exhibited linear PK across 5-10 mg/kg with
relatively low between-subject variability; the full population PK with
body-weight covariates was published separately by Zhou et al. (2012)
and is not refit here.
|
|
Belimumab
(Zhou 2021)
|
Linear two-compartment IV population PK model for belimumab in Chinese
and non-Chinese adult and pediatric patients with systemic lupus
erythematosus (Zhou 2021)
|
|
Benralizumab
(Wang 2017)
|
Two compartment PK model of benralizumab (anti-IL-5Ralpha) in healthy
volunteers and patients with asthma (Wang 2017)
|
|
Betamethasone
(Schoenmakers 2025)
|
Two-compartment population PK model with first-order absorption (no lag
time) for intramuscular betamethasone in pregnant women admitted with
imminent preterm birth, including early-onset pre-eclampsia (eoPE;
diagnosed before 34 weeks gestation). Apparent clearance is multiplied
by 0.617 (a 38% reduction, or ~60% of the non-eoPE clearance) when eoPE
is present; this is the only retained covariate after backward
elimination at P < 0.01. Body weight, BMI, lean body weight, age,
gestational age, number of foetuses, white blood cell counts and CRP
were screened but did not retain after backward elimination.
|
|
Bevacizumab
(Panoilia 2015)
|
Quasi-steady-state target-mediated drug-disposition (TMDD QSS) model for
IV bevacizumab and free VEGF165 in adults with stage IV colorectal
cancer, with fixed allometric body-weight scaling on PK clearances and
volumes (Panoilia 2015, Table 3 TMDD model column)
|
|
Bevacizumab
pk (Papachristos 2020)
|
Two-compartment population PK model for IV bevacizumab in adults with
metastatic colorectal cancer, with allometric weight scaling and ICAM-1
/ VEGF-A genotype covariates (Papachristos 2020, Table 1)
|
|
Bevacizumab
pkpd (Papachristos 2020)
|
Two-compartment population PK plus immediate-response Imax PK/PD model
for IV bevacizumab and free VEGF-A in adults with metastatic colorectal
cancer, with allometric weight scaling and ICAM-1 / VEGF-A genotype
covariates (Papachristos 2020, Table 3)
|
|
Bevacizumab
qss (Papachristos 2020)
|
Quasi-steady-state target-mediated drug-disposition (TMDD QSS) model for
IV bevacizumab and free VEGF-A in adults with metastatic colorectal
cancer, with allometric weight scaling and ICAM-1 / VEGF-A genotype
covariates (Papachristos 2020, Table 2)
|
|
Biib107
(Toukam 2025)
|
Two-compartment population PK model with parallel linear and
Michaelis-Menten elimination, plus direct sigmoidal Emax PK/PD model of
alpha-4 integrin receptor saturation, for BIIB107 (humanized aglycosyl
anti-alpha-4 integrin IgG4 monoclonal antibody) in healthy adult
volunteers (Toukam 2025).
|
|
Brentuximab
(Li 2017)
|
Semimechanistic coupled population PK model for brentuximab vedotin
antibody-drug conjugate (ADC) and its released small-molecule payload
monomethyl auristatin E (MMAE) in adults with CD30-expressing
hematologic malignancies (Li 2017). ADC is described by a linear
3-compartment model with first-order elimination; MMAE by a linear
2-compartment model with first-order elimination. MMAE formation is
driven by (1) proteolytic degradation of the ADC (scaled by a
time-decaying drug-antibody ratio DAR(t) and a cycle-dependent fraction
Fmc = Cycle^Fm) and (2) a first-order deconjugation flux proportional to
the per-ADC MMAE payload above the minimum-detectable DAR. Modeled in
molar units (amount nmol, volume L, concentration pmol/mL = nmol/L = nM)
following the paper’s convention.
|
|
Brentuximab
(Suri 2018)
|
Coupled population PK model for brentuximab vedotin antibody-drug
conjugate (ADC) and its released payload monomethyl auristatin E (MMAE)
in 380 patients with CD30-positive malignancies (Hodgkin lymphoma,
systemic anaplastic large-cell lymphoma, mycosis fungoides, primary
cutaneous ALCL) pooled from six clinical studies including the phase III
ALCANZA study (Suri 2018). ADC is described by a linear 3-compartment
model with zero-order input and first-order elimination; MMAE by a
2-compartment model with first-order elimination, fed from ADC by (a) a
saturable target-binding flux KdTargetADC (initial Target = 1,
irreversibly depleted) and (b) a proteolytic flux
FMexp(-ALFMtad)K10ADC whose conversion fraction
declines as a function of time after the most recent dose. Both fluxes
accumulate in an intermediate Lag compartment that empties to MMAE
central with rate Klag (FM is fixed to 1).
|
|
Brentuximab
(Zhou 2025)
|
Coupled population PK model for brentuximab vedotin antibody-drug
conjugate (ADC) and its released payload monomethyl auristatin E (MMAE)
in pediatric patients (5-18 years) with relapsed/refractory or newly
diagnosed Hodgkin lymphoma or systemic anaplastic large-cell lymphoma
(Zhou 2025). ADC is described by a linear 3-compartment model with
first-order elimination; MMAE by a 2-compartment model with first-order
elimination. ADC -> MMAE flux is the sum of (a) a one-time saturable
target-binding flux KdTargetADC (initial Target = 1 unitless,
irreversibly depleted) and (b) a proteolytic flux
FMexp(-ALFMtad)K10ADC where the conversion fraction
declines as a function of time after the most recent dose. Both fluxes
accumulate in an intermediate Lag compartment that empties to MMAE
central with rate Klag. Final-model parameter values come from Zhou 2025
supplementary Tables S1 (ADC) and S2 (MMAE); equations come from the
NONMEM control streams in Zhou 2025 Supplementary Methods.
|
|
Brivaracetam
(Schoemaker 2017)
|
One-compartment population PK model for oral brivaracetam in paediatric
patients with epilepsy aged 1 month to 16 years (Schoemaker 2017).
First-order absorption, single-compartment distribution, and first-order
elimination, with allometric scaling of CL/F (exponent 0.750 fixed) and
V/F (exponent 1.00 fixed) on lean body weight normalised to a 50 kg
adult typical value. Co-administration of phenobarbital (PB; pooled with
primidone), carbamazepine (CBZ), or valproate (VPA) modify apparent oral
clearance via linear-additive multiplicative factors.
|
|
Brodalumab
(Timmermann 2019)
|
Two-compartment population PK model for brodalumab in adults with
moderate-to-severe plaque psoriasis (Timmermann 2019), with first-order
SC absorption, fixed bioavailability, and combined linear plus
Michaelis-Menten (target-mediated) elimination from the central
compartment.
|
|
Busulfan
(Lawson 2022)
|
Two-compartment IV PK model for once-daily busulfan in pediatric
hematopoietic stem cell transplant recipients with allometric
normal-fat-mass (NFM) scaling, postmenstrual-age maturation on CL, and a
time-associated within-treatment-course CL decline (Lawson 2022).
|
|
Cabazitaxel
(Ferron 2013)
|
Three-compartment population PK model for intravenous cabazitaxel in
patients with advanced solid tumors (Ferron 2013)
|
|
Canakinumab
(AitOudhia 2012)
|
Integrated population PK/PD model of canakinumab (anti-IL-1beta IgG1/k
mAb) in adults with rheumatoid arthritis (Ait-Oudhia 2012).
Two-compartment popPK for total canakinumab is coupled to a
quasi-equilibrium target-binding model with endogenous IL-1beta
(zero-order production ksyn, linear clearance CLL). Predicted free
IL-1beta drives downstream PD: (1) a three-compartment CRP transduction
chain with a power-law stimulation (beta) on free-IL-1beta ratio and an
empirical amplification (gamma) on the input to the third compartment,
and (2) a single-compartment ACR latent variable (ACRL) regulated by a
sigmoid Emax on the drop in free IL-1beta below baseline plus a
first-order placebo build-up; the latent is mapped to ACR20/50/70
response probabilities via a logit transform with a between-subject
random effect. Only body weight was a significant covariate (allometric
on CL, CLL, CLDL, Vc, Vp with reference 70 kg).
|
|
Canakinumab
(Chakraborty 2012)
|
Population pharmacokinetic-binding model for canakinumab (anti-IL-1b
IgG1/k monoclonal antibody) and its endogenous target IL-1b in adult
cryopyrin-associated periodic syndromes (CAPS) patients (Chakraborty
2012). Two physical compartments (central and peripheral) each carry
three species: free canakinumab, free IL-1b, and the canakinumab-IL-1b
complex. Drug, ligand, and complex share the same volumes of
distribution; complex clearance is set equal to free-drug clearance (CLX
= CLD). Distribution between compartments uses two
permeability-surface-area coefficients: PSD for free drug and complex,
PSL for free ligand. Endogenous IL-1b production RLI enters the
peripheral compartment. Drug-ligand binding is solved algebraically
under a quasi-steady-state assumption with dissociation constant KD
(Hayashi 2007 form). Subcutaneous bioavailability F1 was estimated on
the logit scale; this file uses the Sp2/0 cell-line value (commercial
Ilaris). Body weight modifies CLD, VC, VP via centred power covariates;
serum albumin modifies CLD; age modifies SC ka. Two observed analytes:
total canakinumab (free + complex) in ug/mL and total IL-1b (free +
complex) in pg/mL.
|
|
Capecitabine
(Urien 2005)
|
Population PK model for oral capecitabine and its three sequential
metabolites 5’-DFCR (5’-deoxy-5-fluorocytidine), 5’-DFUR
(5’-deoxy-5-fluorouridine), and 5-FU (5-fluorouracil) in 40 adult
patients with metastatic cancer (Urien 2005). Capecitabine PK is a
one-compartment apparent V1/F model with first-order absorption (Ka) and
a lag time; non-transformation elimination CL10/F runs in parallel with
the formation clearance CL12/F to 5’-DFCR. Each metabolite has its own
central compartment with apparent volume fixed to 1 L (only output rate
constants are identifiable in the source NONMEM ADVAN6 fit), so the
chain 5’-DFCR -> 5’-DFUR -> 5-FU -> output is described by
first-order rate constants K23, K34, K40 (paper’s notation). Total
bilirubin (canonical TBILI; source column BILT, umol/L) is the only
retained covariate: power exponent +0.32 on CL10/F and -0.36 on K34,
both centred on the median bilirubin 8.8 umol/L. Inter-individual
variability is reported on TLAG, V1, CL10, K23, K34, and K40; ISV on
CL12 was fixed to 0 and ISV on Ka was deleted in favour of a large
inter-occasion variability on Ka that is not represented in this static
model file (see vignette Errata).
|
|
Carboplatin
(Ekhart 2008)
|
Two-compartment population PK model for free (ultrafilterable)
carboplatin in adult cancer patients (Ekhart 2008)
|
|
Casirivimab
(Lin 2024)
|
Two-compartment population PK model for casirivimab in pediatric and
adult subjects (non-infected, ambulatory or hospitalized
SARS-CoV-2-infected, or household contacts) following IV or SC
administration (Lin 2024, casirivimab arm of the joint casirivimab +
imdevimab popPK model)
|
|
Cediranib
(Li 2017)
|
Two-compartment population PK model for oral cediranib (AZD2171) in
adult cancer patients (Li 2017), with sequential zero- and first-order
absorption (zero-order release into depot followed by first-order
absorption to central), bioavailability fixed to 1, allometric power
scaling on apparent clearance ((WT/73 kg)^0.517 and (Age/59 y)^-0.409)
and on apparent central volume ((WT/73 kg)^0.65), correlated
inter-individual variability between CL/F and Vc/F (correlation 0.839),
independent IIV on Ka, and proportional residual error (rich-sampling
estimate).
|
|
Cefepime
(Jonckheere 2019)
|
Two-compartment population PK model for IV cefepime in critically ill
ICU patients (Jonckheere 2019), updated by simultaneously fitting plasma
+ urine PK from the original Jonckheere 2017 pilot (STDY1) and the
Jonckheere 2019 target-controlled-infusion cohort (STDY2). Total
clearance is the sum of an estimated-creatinine-clearance-driven renal
arm (CL_renal = 2.29 * (eCrCL/60)^0.943 L/h per 70 kg) and a
covariate-free non-renal arm (CL_nonren = 0.795 L/h per 70 kg); all PK
parameters are scaled allometrically with body weight (reference 70 kg,
exponent 3/4 for clearances, 1 for volumes). The structural form encodes
the non-dialysis patient (paper Equations 1-4); a separate CL_dialysis =
4.48 L/h applied during intermittent hemodialysis sessions in the source
dataset is documented in the vignette but not enabled in this model
file.
|
|
Cemiplimab
(Yang 2021)
|
Two-compartment population PK model for cemiplimab (anti-PD-1 IgG4) with
time-varying clearance (sigmoid Emax) in adults with advanced solid
tumors including cutaneous squamous cell carcinoma (Yang 2021)
|
|
Certolizumab
(Wade 2015)
|
One-compartment population PK model with first-order SC absorption and
an additive baseline concentration for certolizumab pegol in adults with
Crohn’s disease (Wade 2015)
|
|
Cladribine
(Savic 2017)
|
Population PK model for cladribine (CdA) in patients with
relapsing-remitting multiple sclerosis (Savic 2017): three-compartment
disposition with first-order oral absorption, separate fasted vs fed (or
unknown food-state) absorption parameters, renal clearance proportional
to Cockcroft-Gault creatinine clearance, and a multiplicative
non-renal-clearance effect of concomitant subcutaneous interferon
beta-1a coadministration.
|
|
Clesrovimab
(Hu 2026)
|
Two-compartment population PK model for clesrovimab in preterm and
full-term infants (Hu 2026)
|
|
Clopidogrel
(Danielak 2017)
|
Joint parent-metabolite population PK model for oral clopidogrel and its
active thiol H4 metabolite (the antiplatelet-active diastereomer) in
adult Caucasian patients undergoing elective coronarography or
percutaneous coronary intervention on chronic clopidogrel 75 mg/day
(Danielak 2017). Clopidogrel is described by a one-compartment model
with first-order absorption (rate constant ka = source k12) and
first-order elimination (CL/F = source CL/F, V/F = source V2/F). The H4
metabolite is described by a one-compartment model with irreversible
first-order formation from clopidogrel central at the rate FM * CL/F *
(clopidogrel central / Vc) and first-order elimination (CL_h4/F = source
Q2/F, V_h4/F = source V3/F). FM was constrained to <= 20% in the
source fit because clopidogrel undergoes extensive first-pass metabolism
to the inactive carboxylic acid (the competing CES1 pathway accounts for
~85% of the absorbed dose); the final estimate is FM = 4.5%. H4 plasma
concentrations were assayed after bromo-3’-methoxyacetophenone
derivatisation of the labile thiol and were adjusted to the mass
equivalent of clopidogrel, so the parent <-> H4 flux carries 1:1
molar / mass-equivalent stoichiometry. Inter-individual variability is
reported on ka, V/F, CL/F, and FM with a covariance between ka and V/F.
The only retained covariate is CYP2C19*2 carriage on FM
(linear-deviation effect, e_cyp2c19_s2_fm = -0.45); carriers convert 45%
less of the absorbed dose to the active H4 metabolite. Bioavailability F
was assumed to be unity (typical value 1, not estimated because no IV
clopidogrel data exist). Residual error is proportional on the
linear-concentration scale for both observed analytes; M3-method
handling was used for samples below the quantitation limit (0.25 ng/mL
for both clopidogrel and H4).
|
|
Concizumab
(Yuan 2019)
|
QSP. Systems PK/PD model for concizumab (humanized anti-TFPI IgG4)
describing binding to both membrane-bound TFPI (mTFPI; non-linear
clearance via receptor-mediated endocytosis) and soluble TFPI (sTFPI;
linear clearance via FcRn-recycled pinocytosis) in a minimal
physiologically-based PK framework with two nested endothelial endosome
compartments. Parameter values for 70 kg adult humans (Yuan 2019 Tables
1-2); the paper also tabulates monkey and rabbit parameter sets.
|
|
Cyclosporin
(Debord 2001)
|
Two-compartment population PK model for oral cyclosporin microemulsion
(Neoral) in stable renal transplant recipients (Debord 2001), with a
gamma-distribution absorption (Savic 2007 analytical transit-compartment
form) feeding the central compartment directly, F fixed to 1, and
population typical values derived from the means of the 21
individually-fitted patients in Table I of the paper.
|
|
Dabigatran
(Liesenfeld 2013)
|
Two-compartment population PK model for oral dabigatran (after
dabigatran etexilate prodrug) in seven end-stage renal disease (ESRD)
subjects undergoing intermittent hemodialysis, with first-order
absorption, absorption lag, an apparent total body clearance (renal +
non-renal), and an apparent dialysis clearance described by the Michaels
equation as a function of blood and dialysate flow rates and a
hemodialyzer mass transfer-area coefficient (Liesenfeld 2013).
|
|
Daclizumab
(Othman 2014)
|
Two-compartment population PK model with first-order subcutaneous
absorption and lag time for daclizumab high-yield process (HYP) in
healthy volunteers (Othman 2014)
|
|
Daclizumab
cd25 (Diao 2016)
|
Sigmoidal Emax PK/PD model of CD25 receptor occupancy on peripheral CD4+
T cells following subcutaneous daclizumab high-yield process (HYP) in
adults with relapsing-remitting multiple sclerosis (Diao 2016). The PD
output is the percentage of CD4+ T cells staining positive for
unoccupied CD25 (i.e., the unbound CD25 fraction). The PK backbone is
the two-compartment, first-order SC absorption + lag model from Othman
2014 (file inst/modeldb/specificDrugs/Othman_2014_daclizumab.R), copied
verbatim with weight-based allometric scaling.
|
|
Daclizumab
cd56bright (Diao 2016)
|
Indirect-response PK/PD model of CD56 bright natural killer (NK) cell
expansion following subcutaneous daclizumab high-yield process (HYP) in
adults with relapsing-remitting multiple sclerosis (Diao 2016).
Daclizumab HYP serum concentration stimulates the zero-order production
rate (Kin) of CD56 bright NK cells (% of all lymphocytes) via a
saturable Smax function; first-order elimination rate Kout is fixed by
the median baseline. The PK backbone is the two-compartment, first-order
SC absorption + lag model from Othman 2014 (file
inst/modeldb/specificDrugs/Othman_2014_daclizumab.R), copied verbatim
with weight-based allometric scaling.
|
|
Daclizumab
treg (Diao 2016)
|
Sigmoidal Emax PK/PD model of regulatory T cell (Treg) reduction
following subcutaneous daclizumab high-yield process (HYP) in adults
with relapsing-remitting multiple sclerosis (Diao 2016). The PD output
is the percentage of Treg (CD4+ CD127low/- Foxp3+) among all CD4+ T
cells; daclizumab HYP serum concentration drives a maximum 60% reduction
via a sigmoidal Emax function. The PK backbone is the two-compartment,
first-order SC absorption + lag model from Othman 2014 (file
inst/modeldb/specificDrugs/Othman_2014_daclizumab.R), copied verbatim
with weight-based allometric scaling.
|
|
Dapagliflozin
(vanderWalt 2013)
|
Semi-mechanistic joint parent-metabolite population PK model for
dapagliflozin and its inactive UGT1A9 glucuronide metabolite
dapagliflozin 3-O-glucuronide (D3OG, identified as M15 in
chromatography) in healthy adults, T2DM subjects with normal or impaired
renal function, and patients with hepatic impairment (van der Walt
2013). Parent: 2-compartment disposition with first-order absorption fed
by a Savic 2007 transit-compartment chain (continuous N estimated
alongside MTT) and a logit bioavailability anchor; three parallel parent
elimination pathways are estimated separately as renal excretion of
unchanged dapagliflozin (CLP_renal, proportional to baseline creatinine
clearance), metabolic formation of D3OG (CLP_M15), and metabolic
clearance to unmeasured metabolites (CLP_other, allometrically scaled
like CLP_M15). Metabolite: 1-compartment with renal elimination CLM
proportional to creatinine clearance. Plasma observations only are
emulated here – the source paper also fitted urine dapagliflozin and
D3OG concentrations simultaneously with a replicate residual-error
structure; see the validation vignette for the urine and
replicate-residual deviations. Covariates: creatinine clearance (CRCL;
IBW-corrected, mL/min) on CLP_M15, CLP_renal, and CLM; AGE on CLP_other;
Child-Pugh Class C (HEPIMP_SEV) on CLP_M15 and V2M; Child-Pugh Class B
or C (HEPIMP_MODSEV) on V3P and CLM; female sex (SEXF) on total CLP and
on CLM; allometric WT scaling on CLP_M15, CLP_other, V2P, V3P, V2M.
|
|
Dapsone
(Hall 2017)
|
One-compartment population PK model with first-order oral absorption for
dapsone in healthy US adults across a wide weight range; covariate
effects on Ka, CL, and Vc are encoded via the published MARS
piecewise-linear basis functions of weight, age, and blood urea nitrogen
(Hall 2017).
|
|
Daratumumab
(Xu 2020)
|
Two-compartment population PK model for intravenous daratumumab
(anti-CD38 IgG1k) in adults with multiple myeloma, with parallel linear
and Michaelis-Menten eliminations from the central compartment. The
maximum velocity of the saturable (target-mediated) elimination decays
mono-exponentially from its baseline value at first-order rate KDES,
mimicking depletion of the CD38 target over weekly 16 mg/kg therapy (Xu
2020 MMY1001 D-Kd / D-KRd cohorts).
|
|
Datopotamab
(Hong 2025)
|
Coupled population PK model for datopotamab deruxtecan (Dato-DXd,
anti-TROP2 antibody-drug conjugate) and its released payload DXd in
adults with advanced solid tumors (Hong 2025). Dato-DXd disposition is a
two-compartment model with parallel linear (CL_lin) and Michaelis-Menten
(Vmax / Km) elimination from the central compartment. DXd is a
one-compartment model whose formation rate equals the total Dato-DXd
elimination rate (linear + nonlinear) scaled by the molecular-weight
ratio (493.5 / 150000) and a time-and-cycle-dependent drug-to-antibody
ratio DAR(tad, CYCLE) = 4 * (0.25 + 0.75 * exp(-beta * tad)) * (1 if
CYCLE = 1 else Factor1). Body weight is included as a mechanistic
covariate with a fixed allometric exponent of 0.75 on Dato-DXd linear
clearance and estimated exponents on Dato-DXd volumes (paper Eq. 8-10)
and on DXd CL/Vc (Eq. 14-15).
|
|
Daunorubicin
(Varatharajan 2016)
|
Population PK model for IV daunorubicin (Dnr) and its primary
carbonyl-reductase metabolite daunorubicinol (DOL) in adult de novo
acute myeloid leukaemia (AML) patients (Varatharajan 2016). Each
component (parent and metabolite) is described by an independent
two-compartment disposition parameterised on apparent clearance, central
volume, and the inter-compartmental rate constants K12 and K21.
Daunorubicin is converted to daunorubicinol via parent elimination (the
model assumes the fraction metabolised fm = 1, so the published DOL CL
and V are ‘apparent’ values that absorb fm). No covariates were retained
in the final structural model; demographic / pharmacogenetic
associations in the paper are reported on post hoc empirical-Bayes
estimates rather than as fixed-effects covariate parameters.
|
|
Dexmedetomidine
(Talke 2018)
|
Three-compartment IV population PK plus effect-compartment sigmoid Emax
PD model for dexmedetomidine-induced peripheral vasoconstriction (ADC
units from finger photoplethysmography) in healthy adult volunteers,
with a priori allometric body-weight scaling on CL, Q2, Q3 (exponent
0.75) and V1, V2, V3 (exponent 1) at a 70 kg reference weight (Talke and
Anderson 2018, Tables 3 and 4)
|
|
Digoxin
(Jelliffe 2014)
|
Two-compartment population PK/PD model of digoxin in adults with
first-order oral absorption, creatinine-clearance-dependent renal
elimination, and a peripheral effect compartment normalized per body
weight (Jelliffe et al. 2014, Ther Drug Monit; structural parameters
carried from Reuning et al. 1973).
|
|
Dilmapimod
(Yang 2016)
|
Three-compartment IV population PK model for dilmapimod (SB-681323, a
p38 MAPK inhibitor) coupled with an empirical indirect-response model
for the inflammatory biomarker C-reactive protein (CRP) in severe-trauma
adults at risk for acute respiratory distress syndrome (Yang 2016). BMI
is a power covariate on CL and Q2. No statistically significant
dilmapimod effect on CRP was retained in the final PD model, so the CRP
component is an empirical post-injury production-decline /
first-order-loss profile that is decoupled from dilmapimod exposure
(Yang 2016 Results section 3.3.1).
|
|
Docetaxel
(Ozawa 2007)
|
Three-compartment IV PK coupled with a modified Friberg-style
semimechanistic-physiological PK/PD model for docetaxel-induced
neutropenia in Japanese cancer patients (Ozawa 2007). The PD layer
extends Friberg 2002 with an additional zero-order input compartment
that captures the transient ANC increase attributable to dexamethasone
premedication; alpha-1 acid glycoprotein modulates the linear
drug-effect slope on the proliferating compartment via a power-law form.
Per-subject baseline ANC is supplied as a covariate and is used to
initialise the proliferation, transit, and circulating compartments.
|
|
Domagrozumab
(Wojciechowski 2022)
|
Quasi-steady-state TMDD population PK/PD model for domagrozumab
(anti-myostatin IgG1) in healthy adult volunteers and pediatric patients
with Duchenne muscular dystrophy (Wojciechowski 2022): two-compartment
IV/SC drug disposition with parallel linear and Michaelis-Menten
elimination, a synthesis-degradation total-myostatin compartment with
drug-mediated internalization, and a study-population covariate
(DIS_DMD) shifting myostatin baseline and turnover.
|
|
Donidalorsen
(Diep 2026)
|
Two-compartment population PK and indirect-response PD model for the
GalNAc3-conjugated antisense oligonucleotide donidalorsen targeting
prekallikrein (PKK) mRNA, fit to pooled data from phase 1 to phase 3
studies in healthy volunteers and patients with hereditary angioedema
(Diep 2026). First-order SC absorption with categorical covariates on ka
(arm vs abdomen/thigh injection site; autoinjector vs vial drug
presentation), allometric scaling of CL/F, Vc/F, Q/F, and Vp/F on total
body weight with paper-estimated exponents, multiplicative
disease-status effects on Vc/F and Q/F, full 5x5 omega block on PK
random effects, and an indirect-response model with donidalorsen-driven
inhibition of PKK production carrying multiplicative disease-status
effects on baseline PKK and IC50.
|
|
Dostarlimab
(Kuchimanchi 2024)
|
Two-compartment population PK model for dostarlimab (anti-PD-1 IgG4)
with sigmoid I_max time-dependent clearance, fitted to GARNET (advanced
solid tumours) plus RUBY Part 1 (primary advanced or recurrent
endometrial cancer with carboplatin-paclitaxel) data (Kuchimanchi 2024)
|
|
Dostarlimab
(Melhem 2022)
|
Two-compartment population PK model for dostarlimab (anti-PD-1 IgG4)
with time-dependent (sigmoid I_max) clearance in adults with advanced
solid tumours (Melhem 2022)
|
|
Doxorubicin
(Kunarajah 2017)
|
Population PK/PD model for IV doxorubicin (3-compartment) with
first-order metabolism to doxorubicinol (1-compartment) and a cardiac
troponin I (cTnI) turnover sub-model in paediatric oncology patients
(Kunarajah 2017). Body surface area enters as a linear factor on every
clearance and volume parameter; age enters as an additional power factor
on doxorubicin clearance. The cTnI turnover sub-model is driven by a
saturable Emax stimulation of cTnI synthesis by the combined doxorubicin
+ doxorubicinol plasma concentration, with the cTnI baseline shifted
linearly by the prior cumulative anthracyclines dose received by the
patient before the first dose analysed.
|
|
Dupilumab
(Kovalenko 2016)
|
Dupilumab exploratory population PK model (Kovalenko 2016; 2-cmt with
parallel linear + Michaelis-Menten elimination)
|
|
Dupilumab
(Kovalenko 2020)
|
Dupilumab PK model (Kovalenko 2020)
|
|
Dupilumab
(Zhang 2021)
|
Two-compartment population PK model for dupilumab in adult and
adolescent patients with asthma (Zhang 2021), with first-order SC
absorption and parallel linear plus Michaelis-Menten elimination from
the central compartment.
|
|
Durvalumab
(Ogasawara 2020)
|
Two compartment PK model of durvalumab (anti-PD-L1) in patients with
hematologic malignancies (Ogasawara 2020)
|
|
EGF
IFN chimera (DoldanMartelli 2013)
|
In vitro (Daudi human Burkitt lymphoma cell line). Mechanistic kinetic
model of an EGF-IFNalpha-2a chimeric ligand binding to EGFR and IFN
receptor on the cell membrane: sequential two-subunit engagement,
receptor lateral diffusion, and internalization (Doldan-Martelli 2013).
Default parameters are wild-type IFN chimera in Daudi-EGFR cells
(overexpressing EGFR ~300x parental); k2on / k2off can be overridden for
K133A and R144A IFN mutants, and R1_0 / R2_0 for parental Daudi cells
(see vignette).
|
|
Elotuzumab
(Ide 2020)
|
Two-compartment population PK model for elotuzumab (anti-SLAMF7
humanized IgG1) in Japanese and non-Japanese patients with multiple
myeloma (Ide 2020); parallel linear and Michaelis-Menten elimination
from the central compartment plus second-order target-mediated
elimination from the peripheral compartment driven by a non-renewable
target pool, with time-varying serum M protein on Vmax.
|
|
Epinephrine
(Abboud 2009)
|
One-compartment population PK model for intravenous epinephrine
(adrenaline) infusion in adults with septic shock, with a constant
endogenous epinephrine production rate (R0) feeding the central
compartment and body weight and SAPS II severity score as power
covariates on clearance (Abboud 2009).
|
|
Epinephrine
(Oualha 2014)
|
Population PK/PD model for continuous IV epinephrine in critically ill
children following cardiopulmonary bypass for repair of congenital heart
defects (Oualha 2014). One-compartment open PK with first-order
elimination plus an endogenous zero-order production rate q0 and
circulating-volume-anchored Vc = 0.08WT; allometric scaling of CL
and q0 on body weight (exponents fixed to 3/4). Hemodynamic Emax
sub-models for heart rate (HR) and the stroke-volume
systemic-vascular-resistance product (SVSVR) with age power effects
on basal HR and SVSVR and a RACHS-1 categorical effect on
SV*SVR_max. Glucose/lactate turnover sub-model: epinephrine stimulates
the zero-order plasma glucose production rate via an Emax function;
plasma lactate is produced at the rate of glucose elimination and itself
follows first-order elimination. kGLY and kLAC are derived at steady
state (Eq. 12-13).
|
|
Eplontersen
(Diep 2022)
|
Two-compartment population PK and indirect-response PD model for the
GalNAc3-conjugated antisense oligonucleotide eplontersen targeting
transthyretin (TTR) mRNA, fit to pooled data from two phase 1 studies in
healthy volunteers (Diep 2022). First-order SC absorption with
site-specific typical ka (arm vs abdomen), allometric scaling on CL by
lean body mass, on Vc/Q/Vp by total body weight, and an
indirect-response model with eplontersen-driven inhibition of TTR
production.
|
|
Eribulin
(vanHasselt 2015)
|
Disease-progression (DP) model for prostate-specific antigen (PSA)
dynamics in metastatic castration-resistant prostate cancer (CRPC)
patients treated with eribulin mesilate (van Hasselt 2015). K-PD
framework: the per-dose predicted eribulin AUC enters a single transient
drug-effect compartment depot that decays with rate KP (fixed to 6000
/day so the effect is nearly instantaneous after each dose); PSA evolves
under a first-order growth rate KG counteracted by an inhibition rate
KD0 multiplied by the K-PD state depot and an exponentially decaying
resistance factor exp(-k_res*t). PSA0, KD0, KG, k_res have correlated
lognormal IIV; proportional residual error on PSA
(log-transform-both-sides). Prior taxane treatment (binary PRIOR_TAXANE)
multiplies PSA0; cumulative number of days of prior taxane treatment
(continuous PRIOR_TAXANE_DAYS) enters KD0 as (1 + NTRT/720)^theta. The
companion parametric Weibull survival sub-model fit in R survreg is
documented in the vignette but not encoded here (not an ODE / nlmixr2
structure).
|
|
Ethanol
(Nemoto 2017)
|
Bayesian population PK model for orally ingested ethanol (alcohol) in 34
healthy Japanese adults (Nemoto 2017). One-compartment model with
first-order absorption and Michaelis-Menten elimination; covariates:
sex, age, body weight, ALDH2 and ADH1B genotypes. Final model fit by a
fully conditional MCMC Bayesian analysis with informative priors derived
from Seng et al. 2014 (Chinese + Indian cohort).
|
|
Etrolizumab
(Moein 2022)
|
Two-compartment population PK model for etrolizumab with first-order SC
absorption and time-decreasing clearance in adults with
moderately-to-severely active ulcerative colitis (Moein 2022)
|
|
Everolimus
(deWit 2016)
|
Two-compartment population PK model with first-order oral absorption for
everolimus 10 mg once-daily in 40 adult patients with advanced thyroid
carcinoma (de Wit 2016). Bioavailability F is structurally fixed at 1
(absolute F unknown), so reported CL, V1, Q, and V2 are apparent (oral /
F). Allometric scaling on apparent clearance (exponent 0.75) and
apparent central volume (exponent 1.0) using a 70 kg reference weight
per the Anderson and Holford theory cited by the paper. Apparent
peripheral volume V2/F was held fixed at 400 L in the final model.
Bioavailability is multiplied by 0.792 in subjects who carry at least
one ABCB1 TTT haplotype (CYP3A / P-gp efflux marker). Inter-occasion
variability on F captures the day-1-vs-day-15 sampling occasion contrast
(CV 19.2%).
|
|
Evinacumab
(Pu 2021)
|
Population PK/PD model for evinacumab in healthy volunteers and adults /
pediatric patients with homozygous familial hypercholesterolemia (Pu
2021): two-compartment PK with first-order SC absorption (with lag time)
and parallel linear plus Michaelis-Menten elimination from the central
compartment, linked to a Type 1 indirect-response model for low-density
lipoprotein cholesterol (LDL-C) where evinacumab inhibits LDL-C
production.
|
|
Evolocumab
(Kuchimanchi 2018)
|
One-compartment population PK model for evolocumab with first-order SC
absorption and parallel linear plus Michaelis-Menten (target-mediated)
elimination from the central compartment, in healthy adults and patients
with hypercholesterolemia (Kuchimanchi 2018)
|
|
Exenatide
(Cirincione 2017)
|
Population PK model for exenatide immediate-release (Cirincione 2017):
two-compartment, parallel linear and Michaelis-Menten elimination,
sequential zero-order then saturable first-order absorption after SC
dosing.
|
|
Factorix
(Koopman 2023)
|
Two-compartment population PK model for recombinant factor IX-Fc fusion
concentrate (rFIX-Fc, eftrenonacog alfa) in haemophilia B patients aged
2-71 years (Koopman 2023)
|
|
Factorviii
(Nestorov 2014)
|
Two-compartment population PK model for recombinant factor VIII Fc
fusion protein (rFVIIIFc, efmoroctocog alfa) in previously treated
patients with severe hemophilia A (Nestorov 2014; final covariate model
with VWF on CL and WT and HCT on V1)
|
|
Farletuzumab
(Farrell 2012)
|
Two-compartment population PK model for farletuzumab (humanized IgG1
anti-folate-receptor-alpha monoclonal antibody) with first-order linear
elimination after IV infusion in women with advanced epithelial ovarian
cancer (Farrell 2012).
|
|
Fentanyl
(Bista 2015)
|
One-compartment population PK model for transdermal fentanyl (Durogesic
patch) in adult cancer patients with first-order absorption from the
patch and allometric body-weight scaling on CL/F and V/F (Bista 2015)
|
|
Fentanyl
(Oosten 2016)
|
One-compartment population PK model for fentanyl administered by
continuous subcutaneous infusion and transdermal matrix patch in adult
cancer patients, with separate first-order absorption for each route,
transdermal lag time, allometric body-weight scaling on CL/F and V/F
(V/F fixed at 280 L), IIV on Ka (sc and td), F (td), and CL/F, IOV on
transdermal Ka multiplexed by occasion, and proportional residual error
(Oosten 2016).
|
|
Ferumoxytol
(Plock 2014)
|
Two-compartment population PK model with Michaelis-Menten elimination
for IV ferumoxytol in healthy adults and adults with chronic kidney
disease (Plock 2014). Encodes the typical non-dialysing-patient form;
the haemodialysis-driven time-varying central volume (VSLOPE) and the
within-session weight-loss effect on V1 (WLO) are described in the
vignette but not enabled in this model file.
|
|
Follitropin
delta (Rose 2016)
|
One-compartment population PK model for FE 999049 (recombinant human
FSH; INN follitropin delta) with first-order subcutaneous absorption
through a single transit compartment and first-order elimination, in 27
healthy pituitary-suppressed female subjects after a single subcutaneous
dose of 37.5-450 IU (2.2-26.3 ug). Body weight enters as an allometric
covariate on apparent clearance (exponent 0.75) and apparent volume of
distribution (exponent 1) with reference weight 65 kg.
|
|
Fosdagrocorat
oc (Shoji 2017)
|
Kinetic-pharmacodynamic (K-PD) model for serum osteocalcin (OC)
bone-formation biomarker following once-daily oral fosdagrocorat
(PF-04171327, a dissociated agonist of the glucocorticoid receptor) or
oral prednisone comparator in adults with rheumatoid arthritis on
background methotrexate (Shoji 2017). Sister model to
Shoji_2017_fosdagrocorat_p1np: identical K-PD structure (virtual K-PD
depot with zero-order Input mg/week and first-order KDE; sigmoid Emax
inhibition of biomarker synthesis with Hill coefficient fixed to 1;
empirical dose-and-time-dependent rebound multiplier; additive
placebo-period slope). For the OC fit Shoji 2017 fixed KDE to the
P1NP-derived estimates and fixed Imax to 1 for both drugs, and used
independent (not block) IIV on KDE, EDK50, and BL.
|
|
Fosdagrocorat
p1np (Shoji 2017)
|
Kinetic-pharmacodynamic (K-PD) model for serum amino-terminal propeptide
of type I collagen (P1NP) bone-formation biomarker following once-daily
oral fosdagrocorat (PF-04171327, a dissociated agonist of the
glucocorticoid receptor) or oral prednisone comparator in adults with
rheumatoid arthritis on background methotrexate (Shoji 2017). A virtual
K-PD depot for the drug (zero-order Input mg/week, first-order
elimination KDE) feeds a sigmoid Emax inhibition of biomarker synthesis
(Hill coefficient fixed to 1); the synthesis rate carries an empirical
dose-and-time-dependent rebound multiplier and an additive linear
placebo-period slope captures the methotrexate-only time trend.
|
|
Fremanezumab
(Fiedler-Kelly 2019)
|
Two-compartment population PK model for fremanezumab (anti-CGRP IgG2
delta-a/kappa mAb) with first-order SC absorption, absorption lag time,
and route-specific central volume / residual error supporting both IV
and SC administration in healthy adults and adults with chronic or
episodic migraine (Fiedler-Kelly 2019).
|
|
Fremanezumab
cm (FiedlerKelly 2020)
|
Population PD exposure-response model relating fremanezumab average
plasma concentration (Cav) to monthly moderate-to-severe headache days
in adults with chronic migraine. Placebo time-course is a Hill (sigmoid)
function in months and the drug effect is a power function of Cav
centered on the population median Cav. Fitted to 5312 monthly
observations from 1361 chronic-migraine patients pooled across the
LBR-101-021 phase 2b and TV48125-CNS-30049 phase 3 studies
(Fiedler-Kelly 2020).
|
|
Fremanezumab
em (FiedlerKelly 2020)
|
Population PD exposure-response model relating fremanezumab average
plasma concentration (Cav) to monthly migraine days in adults with
episodic migraine. Placebo time-course is an exponential growth in
months (predicted reduction = exp(exponent * t)) and the drug effect is
an Emax/EC50 of Cav scaled by individual baseline migraine days. Fitted
to 4444 monthly observations from 1142 episodic-migraine patients pooled
across the LBR-101-022 phase 2b and TV48125-CNS-30050 phase 3 studies
(Fiedler-Kelly 2020).
|
|
Galcanezumab
(Kielbasa 2020)
|
One-compartment population PK model for galcanezumab (humanized IgG
anti-CGRP mAb) with first-order SC absorption, linear elimination, and
allometric body weight scaling on CL/F (Kielbasa 2020)
|
|
Ganciclovir
(Caldes 2009)
|
Two-compartment population PK model for ganciclovir after IV ganciclovir
and oral valganciclovir administration in solid organ transplant
patients infected with cytomegalovirus, with first-order absorption, lag
time, logit-transformed bioavailability, and creatinine-clearance
scaling on CL (Caldes 2009)
|
|
Ganciclovir
(Chen 2021)
|
Two-compartment population PK model for oral ganciclovir (the active
metabolite of valganciclovir) in adult Chinese renal allograft
recipients (Chen 2021), with first-order absorption after a lag time and
a linear creatinine-clearance effect on apparent oral clearance (CL/F).
|
|
Ganciclovir
(Koloskoff 2025)
|
Indirect-response viral turnover PD model for cytomegalovirus (CMV)
viral load decline in pediatric solid-organ and hematopoietic-stem-cell
transplant recipients receiving (val)ganciclovir (Koloskoff 2025). The
model treats the q12h-interval ganciclovir AUC (AUC_0-12) as a
time-varying covariate input AUC_GCV that stimulates first-order viral
degradation through an Emax-EC50 relationship. The upstream popPK that
produces AUC_0-12 (Franck 2021 Bayesian estimator) is NOT included here;
AUC_GCV must be supplied per record by the user, either from the Franck
2021 model or any other AUC source.
|
|
Gantenerumab
(Grimm 2023)
|
Gantenerumab PK model in cynomolgus monkeys (Grimm 2023):
two-compartment plasma PK with brain extracellular distribution across
six brain regions (cerebellum, hippocampus, striatum, cortex, choroid
plexus, CSF).
|
|
Gentamicin
(Llanos 2017)
|
Two-compartment population PK model of gentamicin in pediatric oncology
patients with febrile neutropenia (Llanos-Paez 2017)
|
|
Gentamicin
(Llanos-Paez 2017)
|
Two-compartment population PK model for gentamicin in pediatric oncology
patients (Llanos-Paez 2017 AAC) extended with a renal-cortex
accumulation compartment and an Emax model of relative renal-function
reduction (Llanos-Paez 2017 AAPS J).
|
|
Gentamicin
(Llanos-Paez 2020)
|
Two-compartment IV population PK model for gentamicin in pediatric
oncology and nononcology patients (Llanos-Paez 2020); body composition
is described by normal fat mass (NFM = FFM + Ffat * (TBW - FFM)) with
separate Ffat estimates for CL (0.48) and V1 (0.10) and Ffat fixed to 0
for Q and V2; CL is driven by Holford 2017 GFR-maturation (PMA-based
Hill function) and a power ratio of age/sex-matched physiological mean
serum creatinine (Ceriotti 2008) over individual SCR; oncology cohort
has 15.4% lower V1 and 32.1% lower Q than nononcology.
|
|
Gevokizumab
(Cao 2013)
|
Second-generation minimal physiologically-based PK (mPBPK) model for
gevokizumab in adults (Cao 2013 Model A; clearance from plasma)
|
|
Givosiran
(Ayyar 2024)
|
Mechanistic translational PK model for the GalNAc-siRNA givosiran (Ayyar
& Song 2024) parameterized for human (70 kg adult). 22-ODE system
covering SC depot, central plasma (parent + AS(N-1)3’ active
metabolite), competitive ASGPR receptor binding (free target,
parent-target complex, metabolite-target complex), receptor-mediated
hepatocyte internalization, endolysosomal sequestration / degradation /
endosomal escape, free cytoplasmic siRNA, RISC-loaded siRNA (combined
parent + metabolite), kidney vascular and tissue distribution with a
deep bound pool and GFR elimination - for parent and metabolite.
Pharmacodynamic ALAS1 mRNA silencing (rat-only in the paper) is not
included in the human parameterization.
|
|
Glibenclamide
(Rambiritch 2016)
|
Two-compartment population PK model with first-order oral absorption for
glibenclamide in poorly controlled South African adults with type 2
diabetes (Rambiritch 2016). All disposition parameters are apparent
(CL/F, Vc/F, Vp/F, Q/F); F is not estimated. Concentration data were
log-transformed prior to NONMEM fitting (LTBS), giving an effectively
proportional residual error in linear space. No covariate effects were
retained in the final model.
|
|
Glucarpidase
(Kimura 2023)
|
Modified Michaelis-Menten PK/PD simulation model for glucarpidase (CPG2)
rescue after high-dose methotrexate (Kimura 2023). MTX disposition is
2-compartment IV with renal-only first-order elimination (Kr fixed at
~10% of literature total MTX CL from Fukahara 2008); the remaining
elimination is captured by a saturable hydrolysis term coupled to a
1-compartment IV CPG2 disposition. All structural parameters are
literature-sourced point values (no estimation in the source paper).
|
|
GNbAC1
(Cao 2013)
|
Second-generation minimal physiologically-based PK (mPBPK) model for
GNbAC1 in adults (Cao 2013 Model A; clearance from plasma)
|
|
Guselkumab
(Chen 2022)
|
One-compartment population PK model with first-order SC absorption for
guselkumab (anti-IL-23 human IgG1 lambda mAb) in patients with active
psoriatic arthritis (DISCOVER-1 and DISCOVER-2 phase 3 trials; Chen
2022)
|
|
Guselkumab
(Yao 2018)
|
One-compartment population PK model with first-order SC absorption and
first-order elimination for guselkumab (anti-IL-23 p19 human IgG1-lambda
mAb) in adults with moderate-to-severe plaque psoriasis (pooled phase 2
X-PLORE and phase 3 VOYAGE 1 / VOYAGE 2 trials; Yao 2018)
|
|
Haloperidol
(Franken 2017)
|
One-compartment population PK model for haloperidol in 28 terminally ill
adult palliative-care patients (Franken 2017). Two parallel first-order
absorption routes (oral and subcutaneous) with route-specific absorption
rate constants fixed from literature (Ka oral = 0.236 1/h, Ka SC = 20
1/h derived from intramuscular Tmax = 20 min). Oral bioavailability F =
0.861 is estimated; SC F is assumed to be 1. IIV is included on F, CL,
and Vd; the IIV on F and CL was 99% correlated and is encoded with
correlation fixed to unity (BLOCK pattern). Residual variability is
additive on log-transformed concentrations (LTBS). Covariate analysis
(body weight, age, sex, primary diagnosis, plasma creatinine, urea,
bilirubin, GGT, ALP, ALT, AST, CRP, albumin, concomitant CYP2D6 / CYP3A
inducers and inhibitors, time-to-death) did not retain any covariate in
the final model.
|
|
HL2351
(Ngo 2020)
|
Population PK model for HL2351 (hIL-1Ra-hyFc, ~97 kDa) in healthy adult
Korean men: a quasi-steady-state target-mediated drug disposition
(QSS-TMDD) model coupled with FcRn-mediated recycling. The
injection-site depot feeds a separate distribution space where free drug
equilibrates with FcRn (QSS dissociation constant AKSS1, total FcRn
AFcRn_t); free drug moves to the central compartment either directly
(Ka2) or by FcRn-mediated recycling of the FcRn-drug complex (Krec). In
the central compartment free drug equilibrates with IL1R (QSS
dissociation constant KSS2, total IL1R CIL1R_t), is taken up back to the
distribution space (Kup), exchanged with one peripheral compartment
(Q/F), and eliminated linearly (CL/F). The IL1R-drug complex degrades at
Kdeg2. All drug amounts and concentrations are in nmol / nmol/L; convert
mg dosing using molecular weight 97 kDa (1 mg HL2351 = approximately
10306 nmol).
|
|
Imatinib
(Chien 2022)
|
Two-compartment population PK model for oral imatinib in healthy adult
volunteers (Chien 2022); first-order absorption preceded by a Savic
2007-style analytical transit-compartment chain (mean transit time and
number of transit compartments estimated), first-order elimination, and
an OMEGA BLOCK between the IIV on CL and V1 motivated by their estimated
correlation r > 0.9. No covariates were retained in the final model.
|
|
Imatinib
(Schindler 2017)
|
Joint tumor-dynamics PD model for imatinib-treated GIST liver metastases
(Schindler 2017). Three size metrics (maximum transaxial diameter MTD in
mm, software-segmented actual volume Vactual in mL, calculated
ellipsoidal volume Vellipsoid in mL) follow a logistic tumor-growth
model with a linear DOSE-dependent shrinkage term and a mono-exponential
drug-effect washout (resistance development). Tumor density (Hounsfield
units) follows an indirect-response model in which imatinib linearly
stimulates the loss rate. Each subject can carry up to two liver lesions
(lesion 1 has the larger baseline by convention); the binary covariate
MIX_LARGE_BASE selects between a mixture subpopulation with larger
lesion baselines (MIX_LARGE_BASE = 1, P = 0.348) and a smaller-baseline
subpopulation (MIX_LARGE_BASE = 0). Drug exposure enters via the daily
dose normalized to the median 400 mg, so DOSE is supplied as a
per-record time-varying covariate (in mg/day). The OS and PFS
time-to-event arms of the source publication are not encoded as ODE
compartments here (see vignette Assumptions and deviations).
|
|
Immunoglobulin
(Cheng 2026)
|
Two-compartment population PK model for intravenous immunoglobulin
(IVIG) replacement therapy in pediatric primary-immunodeficiency and
secondary-antibody-deficiency patients (Cheng 2026)
|
|
Infliximab
(Berends 2019)
|
Two-compartment TMDD-QSS population PK/target-dynamics model of
infliximab and free TNF in adults with moderate-to-severe ulcerative
colitis (Berends 2019)
|
|
Infliximab
(Faelens 2021)
|
One-compartment IV population PK model of infliximab in adults with
moderate-to-severe ulcerative colitis (Faelens 2021 adapted model;
baseline-covariate-only re-fit of Dreesen 2019)
|
|
Infliximab
(Fasanmade 2009)
|
Two-compartment population PK model of infliximab (anti-TNF-alpha) in
patients with ulcerative colitis (Fasanmade 2009)
|
|
Infliximab
(Hanzel 2021)
|
Two-compartment population PK model of subcutaneous and intravenous
infliximab CT-P13 (biosimilar) in adults with Crohn’s disease and
ulcerative colitis (Hanzel 2021)
|
|
Inotuzumab
(Wu 2024)
|
Two-compartment population PK model for inotuzumab ozogamicin in
pediatric and adult patients with relapsed/refractory B-cell precursor
acute lymphoblastic leukemia (BCP-ALL) and adult patients with B-cell
non-Hodgkin’s lymphoma (NHL); linear plus time-dependent
(target-mediated) clearance with covariate effects on CL_SS, Vc,
CL_TIME, and kdes (Wu 2024, ITCC-059 pediatric trial pooled with 11
adult studies).
|
|
Ipilimumab
(Sanghavi 2020)
|
Two-compartment population PK model for intravenous ipilimumab
(anti-CTLA-4 IgG1) with time-varying clearance via a sigmoid Emax
function in patients with advanced solid tumors receiving ipilimumab
alone or in combination with nivolumab (Sanghavi 2020)
|
|
Isatuximab
(Brillac 2025)
|
Two-compartment population PK model with linear elimination for
isatuximab in pediatric and adult patients with relapsed/refractory
acute leukemias (Brillac 2025)
|
|
Isatuximab
(Fau 2020)
|
Two-compartment population PK model for intravenous isatuximab
(anti-CD38 IgG1) in adults with relapsed/refractory multiple myeloma,
with parallel time-varying linear and Michaelis-Menten eliminations from
the central compartment (Fau 2020). The linear clearance follows a
sigmoidal Emax decay from baseline to steady state; the magnitude of the
decay differs by multiple-myeloma immunoglobulin type.
|
|
Itraconazole
(Hennig 2006)
|
Population PK model for oral itraconazole and its active metabolite
hydroxy-itraconazole in paediatric cystic-fibrosis and
bone-marrow-transplant patients (Hennig 2006). One-compartment parent +
one-compartment metabolite with first-order absorption, first-order
metabolic conversion (fm fixed to 1), allometric weight scaling on
parent CL/F (0.75) and Vd/F (1.0), and formulation-specific ka and
relative bioavailability for capsule vs oral solution.
|
|
Itraconazole
(Hennig 2007)
|
Two-compartment population PK model for oral itraconazole and its
one-compartment hydroxy-itraconazole metabolite in adult cystic fibrosis
patients (Hennig 2007), with first-order absorption from a depot,
formulation-specific absorption rate constants and bioavailability for
capsule vs. oral solution selected by the binary FORM_CAPSULE covariate,
and a single absorption lag-time shared across both formulations. The
fraction of itraconazole metabolised to hydroxy-itraconazole is fixed to
1; metabolite parameters are reported as CL_m/(Ff_m) and
V_m/(Ff_m).
|
|
Ixazomib
(Gupta 2017)
|
Three-compartment population pharmacokinetic model for the oral
proteasome inhibitor ixazomib (Ninlaro) in 755 adult patients with
multiple myeloma, lymphoma, solid tumours, or light-chain amyloidosis
pooled across ten phase I, I/II, and III trials including TOURMALINE-MM1
(Gupta 2017). First-order linear absorption with a 13 min lag time
describes oral dosing; intravenous and oral data share the same
disposition kinetics. Inter-individual variability is estimated on
clearance, bioavailability F, and the second peripheral volume V4, with
a strong (82%) correlation between log CL and log F. Body surface area
on V4 (reference 1.87 m^2, exponent 2.06) is the only retained
covariate; sex, age, race, mild/moderate renal impairment, mild hepatic
impairment, smoking status, and CYP-modulatory concomitant medications
had no clinically relevant effect on systemic exposure. Residual error
is additive on log-transformed concentration with a
time-after-dose-varying standard deviation declining exponentially from
SD1 = 1.90 to SD0 = 0.46 with rate KSD = 0.84/h (Karlsson 1995 model 3).
|
|
Ixekizumab
(Jackson 2022)
|
Two-compartment linear population PK model for subcutaneous ixekizumab
in paediatric patients with moderate-to-severe plaque psoriasis
(IXORA-PEDS; Jackson 2022)
|
|
Ketorolac
(Valitalo 2017)
|
Three-compartment population PK model for IV ketorolac in adults,
jointly fit to R-ketorolac and S-ketorolac plasma concentrations after
racemic IV dosing in women at delivery, postpartum women, nonpregnant
women, and men (Valitalo 2017 BJCP). Body-weight allometric scaling on
clearance and volumes (reference 71 kg) plus proportional
pregnancy-at-delivery and male-sex effects on clearance (and
pregnancy-at-delivery on volumes), shared between enantiomers.
|
|
Lamivudine
(Archary 2019)
|
One-compartment population PK model for lamivudine in severely
malnourished HIV-infected children (Archary 2019); CL/F matures with age
via a sigmoid Emax function, Vc/F decreases linearly with serum
triglyceride, and ka steps up between day 1 and day 14 of antiretroviral
treatment
|
|
Lampalizumab
(Le 2015)
|
Combined ocular-serum target-mediated drug-disposition (TMDD) model with
quasi-steady-state binding approximation for intravitreally administered
lampalizumab (anti-complement factor D Fab) and total complement factor
D (CFD) in adults with geographic atrophy secondary to age-related
macular degeneration. Vitreous humor is the dosing compartment (depot)
and the site of drug-target binding; aqueous humor lampalizumab and
aqueous humor total CFD observations are derived from vitreous via
constant partition coefficients; serum lampalizumab is the central
elimination compartment with linear first-order clearance. Age and
female sex modify ocular and systemic elimination rates respectively (Le
2015 Table 1, Eq. 1-7).
|
|
Lanreotide
(Buil-Bruna 2015)
|
One-compartment population PK model with parallel first- and zero-order
subcutaneous absorption for lanreotide Autogel/Depot in patients with
gastroenteropancreatic neuroendocrine tumors (Buil-Bruna 2015). A linear
effect of body weight on apparent clearance and a small categorical
effect of sex on the first-order absorbed fraction are retained;
absolute bioavailability F is not identifiable and is structurally
anchored at 1, so apparent CL/F and Vd/F are reported. Concentrations
are predicted in ng/mL; residual error is additive on the
log-transformed observations (LTBS), mapped to proportional in linear
space.
|
|
Lebrikizumab
(Zhu 2017)
|
Lebrikizumab population PK model (Zhu 2017): two-compartment model with
first-order absorption after SC dosing in adults with moderate-to-severe
asthma.
|
|
Lenvatinib
(Gupta 2016)
|
Three-compartment population PK model for lenvatinib in healthy subjects
and patients with cancer (Gupta 2016). Simultaneous first-order plus
zero-order oral absorption into the central compartment, linear
elimination, and covariate effects of body weight (allometric on CL/F
and Q/F with exponent 0.75 and linear on V/F), CYP3A4 inducers (+30
percent on CL/F), CYP3A4 inhibitors (-7.8 percent on CL/F), serum
albumin < 30 g/L (-16.3 percent on CL/F), alkaline phosphatase >
ULN (-11.7 percent on CL/F), healthy-subject cohort (+15 percent on CL/F
vs cancer patients), and capsule vs tablet formulation (relative
bioavailability 0.896).
|
|
Ligelizumab
(Bienczak 2025)
|
Two-compartment population PK model for ligelizumab in adolescent and
adult patients with chronic spontaneous urticaria and healthy adult
volunteers (Bienczak 2025)
|
|
Linagliptin
(Retlich 2015)
|
Two-compartment population PK model with concentration-dependent
(saturable) binding of linagliptin to dipeptidyl peptidase-4 in both
central and peripheral compartments, coupled with a population sigmoid
Emax PK/PD model relating total linagliptin plasma concentration to
plasma DPP-4 activity, in adults with type 2 diabetes mellitus (Retlich
2015 Tables 4 and 5).
|
|
Linezolid
(Tsuji 2017)
|
Population PK/PD model for linezolid in hospitalized adult and pediatric
patients with MRSA or gram-positive cocci infections (Tsuji 2017). PK is
a two-compartment model with first-order oral absorption and an additive
renal-plus-non-renal clearance structure (CL = CL_nonren + CL_renal *
RF, where RF = CrCl / 100 mL/min/70 kg standardized to 70 kg by
allometry); plasma total and unbound concentrations are modelled
simultaneously with an estimated fraction-unbound (FU = 0.823) linking
the two. PD is a Friberg-style semi-mechanistic platelet turnover model
(one proliferating compartment, three transit compartments, one
circulating compartment) with an empirical (PLTZERO/PLT)^gamma feedback
term and a published mixture model of two thrombocytopenia mechanisms:
linear inhibition of platelet synthesis (PDI, 97% of patients, SLOPE on
RFORM) and saturable stimulation of platelet elimination (PDS, 3% of
patients, Emax on Kcirc), selected per subject by the binary covariate
MIX_PDI.
|
|
Liraglutide
(CarlssonPetri 2021)
|
Liraglutide PK model in adolescents (Carlsson Petri 2021)
|
|
Lopinavir
(Archary 2018)
|
One-compartment first-order-absorption population PK model for oral
lopinavir/ritonavir in severely malnourished HIV-infected children, with
FFM allometric scaling and a linear total-cholesterol effect on apparent
clearance (Archary 2018).
|
|
Lumefantrine
(Kloprogge 2013)
|
Population PK model for oral lumefantrine in pregnant and non-pregnant
women with uncomplicated Plasmodium falciparum malaria in Uganda after
the standard fixed-dose oral artemether-lumefantrine treatment
(Kloprogge 2013). Flexible five-compartment transit absorption chain
into a two-compartment disposition model with relative bioavailability
F1 fixed at 1, log-normal IIV on CL / Vp / MTT / F, and covariate
effects of pregnancy on intercompartmental clearance (-36.5%,
categorical) and body temperature on mean absorption transit time
(+16.5% per degC over 36.0-39.8 degC, linear-deviation centered at the
cohort median 36.9 degC).
|
|
Lumiracoxib
rat (VasquezBahena 2009)
|
Preclinical (rat). Two-compartment population PK plus indirect-response
PK/PD model for the antinociceptive effect of oral lumiracoxib in
carrageenan-induced thermal hyperalgesia in female Wistar rats
(Vasquez-Bahena 2009). PK: first-order absorption with lag time and
dose-dependent relative bioavailability. PD: time-variant (gamma
function) carrageenan-induced COX-2 synthesis with first-order COX-2
degradation; lumiracoxib reversibly inactivates COX-2 via a competitive
binding model (COX-2_act = KD * COX-2 / (KD + Cp)). The level of
inflammatory mediators (MED) equals the active COX-2 amount and drives
the paw withdrawal latency response LT = LT0 / (1 + MED).
|
|
Luspatercept
(Chen 2020)
|
One-compartment population PK model for luspatercept (activin receptor
type IIB / IgG1 Fc-fusion) in adults with anemia due to myelodysplastic
syndromes (Chen 2020), with first-order subcutaneous absorption,
first-order linear elimination parameterised in CL/F and V1/F, body
weight + age + baseline albumin power covariates on CL/F, and body
weight + baseline albumin power covariates on V1/F.
|
|
M3g
rat (Xie 2000)
|
Preclinical (rat, male Sprague-Dawley). Blood-brain barrier (BBB)
distributional model for morphine-3-glucuronide (M3G) in rat as
published by Xie et al. (2000, Br J Pharmacol): a one-compartment plasma
PK driven by an unbound systemic clearance CL_u = 3.8 mL/min from the
paper’s Model A, coupled to a two-compartment brain model (brain 1 =
sampled brain extracellular fluid via striatal microdialysis, brain 2 =
deeper redistribution compartment) with asymmetric BBB exchange
(separate unbound influx CL_u,in and efflux CL_u,out across the BBB) and
a symmetric intercompartmental clearance Q_br between the two brain
compartments. The model captures a probenecid-sensitive organic-anion
transport contribution to BBB influx: CL_u,in is 1.55-fold higher under
co-administered probenecid (CONMED_PROBENECID = 1) while CL_u,out, Q_br,
and the two brain volumes are unchanged.
|
|
MagnesiumSulfate
(Salinger 2013)
|
One-compartment population PK model of magnesium sulphate (MgSO4-7H2O)
with first-order intramuscular absorption, IV dosing into the central
compartment, and an endogenous baseline magnesium term added to the
administered drug, in pregnant women with pre-eclampsia (Salinger 2013).
|
|
MBG453
(Xu 2023)
|
Two-compartment population PK model for sabatolimab (MBG453, anti-TIM-3
IgG4) with parallel linear and Michaelis-Menten elimination from the
central compartment, fit to pooled adult patients with advanced solid
tumors and hematologic malignancies (Xu 2023).
|
|
MEDI528
(Cao 2013)
|
Second-generation minimal physiologically-based PK (mPBPK) model for
MEDI-528 in adults (Cao 2013 Model A; clearance from plasma)
|
|
Medi7836
(Hood 2021)
|
Population PK-PD binding model for MEDI7836 (anti-IL13 IgG1 lambda-YTE
mAb) in healthy adult males (Hood 2021): two-compartment SC PK with
first-order absorption, ADA-on-CL covariate, plus IL13 turnover, fixed
Kon/Koff binding to MEDI7836:IL13 complex, complex distribution sharing
CL/Q/V3 with parent drug, and a serum PD observation modelled as the
molar sum of free IL13 and a small fraction of complex.
|
|
Mepolizumab
(Cao 2013)
|
Second-generation minimal physiologically-based PK (mPBPK) model for
mepolizumab in adults (Cao 2013 Model A; clearance from plasma)
|
|
Meropenem
(Shekar 2014)
|
Two-compartment IV population PK model for meropenem in critically ill
adult patients on extracorporeal membrane oxygenation (ECMO) and
historical critically ill control patients with sepsis, with a piecewise
covariate on clearance that switches between a fixed RRT-cohort CL and a
Cockcroft-Gault-CrCL-driven non-RRT CL (Shekar 2014)
|
|
Methotrexate
(Taylor 2020)
|
Three-compartment population PK model for intravenous high-dose
methotrexate (5 or 8 g/m^2 over 24 h IV infusion) in pediatric NOPHO
ALL2000 / ALL2008 patients with acute lymphoblastic leukemia;
BSA-normalized PK parameters (reference 1.73 m^2) and a time-varying
serum creatinine power effect on clearance (reference 29 umol/L)
implemented as the default population PK model behind the MTXPK.org
clinical decision support tool (Taylor 2020)
|
|
Methylphenidate
(Teuscher 2015)
|
Pediatric population PK model for methylphenidate hydrochloride
extended-release multilayer beads (MPH-MLR, Aptensio XR) after a single
oral dose, parameterized as a two-input, one-compartment,
first-order-elimination structure: a fast-release (IR) depot delivers a
fraction F1 of dose with first-order absorption rate Ka1, a slow-release
(ER) depot delivers the remaining 1 - F1 with first-order rate Ka2 after
an absorption lag tlag, and the central compartment eliminates linearly
via clearance CL and apparent volume V. Body weight enters CL via a
power covariate CL = CL_TV * WT^theta (Eq 4). Between-individual
variability is retained on CL and V; IIV on Ka1, Ka2, F1, and tlag was
not in the final pediatric fit (Table 1). The companion
exposure-response analysis maps simulated Cmax to change-from-baseline
ADHD-RS-IV total score via the Emax model E = Emax * Cmax / (EC50 +
Cmax) with Emax = -34.96 and EC50 = 5.77 ng/mL (Table 2); the PD step
lives outside the ODE system because the published mapping uses a
per-period Cmax, not the instantaneous central concentration. The
vignette reproduces the full PK simulation, NCA, and Cmax-to-ADHD-RS-IV
exposure-response.
|
|
MHD
rat (Clinckers 2008)
|
Preclinical (rat). Population PK model for 10,11-dihydro-10-hydroxy-
carbamazepine (MHD), the active metabolite of oxcarbazepine, in male
Wistar rat plasma and hippocampal extracellular fluid (Clinckers 2008).
One-compartment central disposition (V2) with combined zero-order
(fraction F1 of dose over duration D2) and lagged first-order (1 - F1,
ka with lag ALAG1) absorption after intraperitoneal bolus, coupled to a
biophase / effect compartment (V3) reached via inter-compartmental rate
constants k23 and k32. Acute focal pilocarpine-induced seizure activity
and local intrahippocampal verapamil (efflux-transporter blockade) each
shrink the biophase volume (V3a -> V3b under seizure; V3a -> V3c
under verapamil); plasma kinetics are unaffected.
|
|
Micafungin
(Martial 2017)
|
Two-compartment population PK model for IV micafungin in adult
intensive-care-unit patients with suspected or proven fungal infection
(Martial 2017). Body-weight allometric scaling (fixed exponents 0.75 on
CL and Q, 1 on V1 and V2; 70 kg reference), log-normal IIV on CL and V1
(encoded as diagonal; the source reports a qualitative non-zero
correlation but no numerical covariance), and a proportional residual
error. No covariates were retained in the final model (only weight via
the a-priori allometric structure).
|
|
Midazolam
(Brill 2014)
|
Three-compartment population PK model for midazolam with two equalized
peripheral volumes and a three-transit-compartment first-order oral
absorption chain (Ka = Ktr), supporting oral and intravenous dosing, in
20 morbidly obese patients (mean total body weight 144 kg, range
112-186; mean BMI 47, range 40-68) and 12 non-obese healthy volunteers
(mean total body weight 76 kg, mean BMI 22). Total body weight enters as
a linear covariate on central volume (reference 127 kg) and a power
covariate on peripheral volume (reference 127 kg); morbid-obesity status
(BMI > 40) shifts oral bioavailability up and the transit absorption
rate down.
|
|
Miridesap
(Sahota 2015)
|
Target-mediated drug disposition (TMDD) PK/PD model for CPHPC
(miridesap, GSK2315698, Ro 63-8695) and serum amyloid P (SAP) in healthy
volunteers (study CPH113776) and patients with systemic amyloidosis
(study CPH114527). Two-compartment PK for CPHPC (IV plus first-order
subcutaneous depot); two-compartment turnover model for SAP with
first-order endogenous production and elimination; bimolecular CPHPC +
free SAP -> complex binding treated as effectively irreversible (KOFF
set to zero because the complex internalisation rate is much faster than
the dissociation rate). Final-model covariates (Sahota 2015 Eq. 1 and
Eq. 2): creatinine clearance modifies CPHPC clearance below an 80 mL/min
threshold; hepatic amyloid involvement multiplies SAP intercompartmental
clearance Q4; whole-body amyloid load (categorical 0-3) multiplies SAP
peripheral volume V4 in two cumulative steps; biological sex multiplies
baseline plasma SAP.
|
|
Mirikizumab
(Chua 2025)
|
Two-compartment population PK model for mirikizumab (anti-IL-23p19 IgG4
mAb) in patients with moderately-to-severely active Crohn’s disease
(Chua 2025 VIVID-1 phase 3)
|
|
Mogamulizumab
(Mukai 2019)
|
Two-compartment population PK model for mogamulizumab in adults with
cutaneous T-cell lymphoma or adult T-cell lymphoma (Mukai 2019)
|
|
Monalizumab
(Hwang 2023)
|
Two-compartment population PK model for monalizumab (anti-CD94/NKG2A
IgG4) in patients with advanced solid tumors or squamous cell carcinoma
of the head and neck (Hwang 2023)
|
|
Morphine
(deHoogd 2017)
|
Joint parent-metabolite population PK model for morphine and its two
glucuronide metabolites (M3G, M6G) in 20 morbidly obese adults
(post-gastric-bypass) and 20 healthy adult volunteers (de Hoogd 2017).
Morphine: three-compartment IV model with total body weight (TBW)
covariate on the second peripheral volume V5M. Non-glucuronide morphine
clearance is structurally fixed at 35% of total morphine CL in a 70-kg
healthy adult. M3G and M6G are each one-compartment models fed by
formation-delay transit chains (n = 5 for M3G, n = 2 for M6G); VM3G =
VM6G is a structural equality. TBW covariates apply to CLF M6G, the M3G
transit rate Ktr, M3G elimination CL, and M6G elimination CL, all
power-form normalised to a reference of 98.5 kg (population median).
Proportional residual error is reported separately for the healthy-
volunteer cohort and the morbidly obese cohort, selected via the binary
indicator DIS_OBESE_MORBID.
|
|
Morphine
(Franken 2015)
|
Joint parent-metabolite population PK model for morphine and its two
glucuronide metabolites (M3G, M6G) in 47 terminally ill adult palliative
care patients (Franken 2015). Morphine: two-compartment disposition with
three parallel first-order absorption routes (subcutaneous bolus,
immediate-release oral liquid, controlled-release oral tablet) using
route-specific fixed absorption rate constants; oral bioavailability F
is estimated (SC F assumed 1). M3G and M6G are each one-compartment
models fed by fixed-fraction transformation of morphine clearance (Fm1 =
0.55 for M3G, Fm2 = 0.10 for M6G, both fixed from literature). Morphine
clearance decreases exponentially as time-to-death (TTD, days)
approaches zero. Metabolite clearance depends on estimated glomerular
filtration rate (eGFR, MDRD four-variable formula) and serum albumin via
shared power-form covariate exponents. Residual variability was reported
as additive error on the log-transformed observation (LTBS).
|
|
Morphine
(Pierre 2017)
|
Joint parent-metabolite population PK model for IV morphine and its
primary glucuronide metabolite morphine-3-glucuronide (M3G) in 14
healthy adults and 7 patients with biopsy-confirmed nonalcoholic
steatohepatitis (NASH) following a single 5 mg morphine sulfate IV
infusion (Pierre 2017). Morphine is described by a three-compartment
disposition (central + two peripherals) with parallel renal (CL_M_R) and
non-renal (CL_M_NR) clearances; the entire non-renal clearance is
assumed to lead to M3G formation via a single liver transit compartment
with first-order rate constant k_trans. M3G is described by a
one-compartment model with a single total clearance (CL_M3G). Cumulative
urinary morphine and M3G amounts are tracked as elimination-amount
compartments. Total body weight enters all CL/Q and V parameters a
priori with fixed allometric exponents (0.75 and 1, respectively)
referenced to 70 kg. The NASH severity score (NASF; combined NAFLD
activity score and fibrosis staging, 0-12) is the only additional
covariate retained in the final model; it acts on M3G clearance through
a linear effect on the natural logarithm of (NASF / 4) for NASF >= 4
and is identically zero for NASF < 4 so that healthy and benign-NAFLD
subjects (NASF < 5) recover the typical CL_M3G.
|
|
Moxifloxacin
(Hong 2015)
|
Sequential population PK + PD (QT-interval) model for single-dose oral
moxifloxacin (400 mg or 800 mg, Avelox tablets) in healthy adult Korean
male volunteers (Hong 2015): a two-compartment first-order absorption PK
model with a lag time and a dose-dependent absorption rate constant
(different Ka for 400 mg vs 800 mg), followed by an individually
corrected QT-interval PD model that adds two mixed-effect cosine
circadian components (24 h and 6 h), a first-order-decaying placebo
(water-intake) effect, and an Emax drug effect on QT prolongation.
|
|
MRNA3927
(Attarwala 2023)
|
Preclinical (mouse, rat, cynomolgus monkey; allometrically scalable to
humans). Translational semi-mechanistic PK and PK/PD model for
mRNA-3927, an LNP-encapsulated dual mRNA encoding propionyl-CoA
carboxylase (PCC) subunits PCCA and PCCB. PK: 3-compartment
plasma1-tissue-plasma2 redistribution (V shared between the two plasma
compartments; V and V2 fixed at the mouse reference and scaled
allometrically) with body-weight allometric scaling of clearances (mouse
reference 0.025 kg; estimated exponents cla on CL12/CL32 and clb on
CL23/CL20). PD: liver PCC protein 2-compartment indirect-response model
driven by an effect compartment linked to plasma mRNA, with synthesis
linear in effect-compartment mRNA concentration and first-order
degradation. Three downstream biomarkers (2-methylcitrate,
3-hydroxypropionate, C3/C2 carnitine ratio) follow direct sigmoidal Imax
suppression by liver PCC protein with Imax fixed at 0.999.
|
|
Nalmefene
(Kyhl 2016)
|
Population PK model for nalmefene in healthy volunteers (Kyhl 2016):
two-compartment model with first-order absorption after oral dosing,
separate absorption rates for tablet and solution formulations, and a
link to mu-opioid receptor occupancy.
|
|
Nalmefene
(Laffont 2024)
|
Population PK model for intranasal (IN) nalmefene HCl in healthy adult
volunteers (Laffont 2024): two-compartment model with linear
elimination, parallel zero-order plus lagged first-order absorption, and
allometric body-weight scaling on apparent clearance.
|
|
Naloxone
(Laffont 2024)
|
Population PK model for intranasal (IN) naloxone HCl in healthy adult
volunteers (Laffont 2024): two-compartment model with linear elimination
and parallel zero-order plus lagged first-order absorption; Q/F and Vp/F
fixed to literature values from Yassen 2007.
|
|
Necitumumab
(Long 2017)
|
Two-compartment population PK model for necitumumab in cancer patients
(Long 2017), with IV infusion input and parallel linear plus
Michaelis-Menten (target-mediated) elimination from the central
compartment and allometric weight scaling on CL, Q, V1, and V2.
|
|
Nimotuzumab
(Castro-Surez 2020)
|
Semi-mechanistic two-compartment QSS TMDD population PK model for
nimotuzumab (anti-EGFR humanized IgG1) in adults with autosomal dominant
polycystic kidney disease (Castro-Suarez 2020); EGFR binding represented
in both central (Rtot) and peripheral (Rtotp) compartments under
quasi-steady-state, plus a turnover mediator that stimulates
non-specific clearance via a sigmoid Emax of free central nimotuzumab.
|
|
Nipocalimab
(Valenzuela 2025)
|
Integrated PK/RO/IgG/MG-ADL QSS TMDD model for nipocalimab in healthy
adults and generalized myasthenia gravis (Valenzuela 2025)
|
|
Nirsevimab
(Clegg 2024)
|
Two-compartment population PK model for nirsevimab in preterm and term
infants (Clegg 2024)
|
|
Nivolumab
(Bajaj 2017)
|
Two-compartment population PK model for nivolumab (anti-PD-1 IgG4) with
time-varying clearance (sigmoid Emax) in patients with advanced solid
tumors (Bajaj 2017)
|
|
Nivolumab
(Zhang 2019)
|
Two-compartment population PK model with time-varying clearance for
intravenous nivolumab (anti-PD-1 IgG4) in adults with advanced solid
tumors, alone or in combination with ipilimumab or chemotherapy (Zhang
2019)
|
|
Nutlin3a
(Zhang 2011)
|
Preclinical (mouse). Whole-body PBPK model for nutlin-3a (MDM2
inhibitor) in adult C57BL/6 mice after intravenous and oral
administration (Zhang et al. 2011, DMD). Thirteen physiological tissue
compartments (adipose, adrenal gland, bone marrow, brain, intestine +
lumen, liver, lung, muscle, retina, spleen, vitreous, residual
diffusion-limited tissue + residual vascular space) with arterial and
venous blood pools (75/25 split of total blood volume).
Perfusion-limited tissues use a partition coefficient K_i; the eye is
modelled as retina + vitreous coupled by a permeability-surface-area
product PA_VIT; the residual compartment is diffusion-limited (5%
vascular space, 95% tissue, coupled by PA_RES). Elimination is combined
linear (hepatic, k_e) and saturable Michaelis-Menten (arterial,
V_max/K_m). Oral absorption is first-order from an intestinal lumen
depot. Plasma protein binding is reported (B_max = 286 uM, K_A = 0.085
1/uM, Langmuir form) but is only used for an unbound-concentration
derivation that the paper applies to tissue exposure / IC50 comparisons,
not to the elimination ODEs; the ODE system operates on total
concentrations. The model is intended for typical-value simulation.
|
|
Obinutuzumab
(Gibiansky 2014)
|
Two-compartment population PK model of obinutuzumab (GA101,
glycoengineered type II anti-CD20 mAb) in adults with chronic
lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL); clearance is
the sum of a time-independent component CL_inf and a mono-exponentially
decaying time-dependent component CL_Texp(-kdestime), with
histology (CLL / BCL / DLBCL / MCL), baseline tumor size, body weight,
and sex as covariates (Gibiansky 2014).
|
|
Ofatumumab
(Yu 2022)
|
Population PK / B-cell-count model for subcutaneous ofatumumab in adults
with relapsing multiple sclerosis (Yu 2022)
|
|
Olaratumab
(Mo 2018)
|
Two-compartment population PK model with linear clearance for olaratumab
in patients with advanced or metastatic cancer (Mo 2018)
|
|
Olokizumab
(Kretsos 2014)
|
Two-compartment population PK with linear elimination and SC first-order
absorption (depot, central, peripheral1) plus effect-compartment
fractional sigmoid Imax PD model for C-reactive protein (CRP)
suppression in mild-to-moderate rheumatoid arthritis patients receiving
single-dose IV or SC olokizumab (anti-IL-6 monoclonal antibody, IgG4,
CDP6038). Final-analysis estimates from Kretsos et al. 2014 Table 1
(Final column), pooling first-in-human (healthy volunteers, Hickling
2011) and first-in-patient (Cohorts 1+2, n=27 active-treatment subjects)
data. The PK observation model adds a per-subject endogenous anti-IL-6
baseline (‘endo’) as an additive offset on the observed OKZ
concentration. Body weight was reported as a significant covariate on CL
and central volume (paper Discussion) but its functional form /
exponents were not reported in main text or supplement; the body-weight
covariate effect is omitted here – see vignette Assumptions.
|
|
Olprinone
(Kunisawa 2014)
|
Two-compartment intravenous population PK model for olprinone (a
phosphodiesterase III inhibitor) in healthy adult Japanese male
volunteers with body-weight normalization on CL, Vc, Q and Vp (Kunisawa
2014)
|
|
Omalizumab
(Hayashi 2007)
|
Mechanism-based binding population PK/PD model for omalizumab and IgE in
Japanese atopic-asthma patients (Hayashi 2007). Three serum entities
(free omalizumab, free IgE, and the omalizumab-IgE complex) each carry
their own clearance and volume of distribution and are coupled through
instantaneous-equilibrium binding (law of mass action) with a
concentration-dependent dissociation constant. Body weight modifies
omalizumab CL and Vd; baseline IgE modifies IgE CL and IgE production
rate. Subcutaneous absorption is first-order. Disposition parameters are
reported as apparent (divided by SC bioavailability f). Three observed
quantities: total omalizumab (ug/mL), total IgE (ng/mL), and free IgE
(ng/mL).
|
|
Ontamalimab
(Wang 2020)
|
Two-compartment population PK model for ontamalimab (SHP647), a fully
human IgG2 anti-MAdCAM-1 monoclonal antibody, in adults with
moderate-to-severe ulcerative colitis or Crohn’s disease (Wang 2020),
with first-order SC absorption, absorption lag time, parallel linear and
Michaelis-Menten elimination from the central compartment, and
allometric weight scaling on CL, Vc, Q, Vp, and Vmax.
|
|
Ormutivimab
(Zhang 2022)
|
Time-dependent population pharmacodynamic Emax model for rabies virus
neutralizing antibody (RVNA) activity after rabies vaccination in
healthy Chinese adults, with a categorical drug-product covariate that
contrasts Ormutivimab (rHRIG, a recombinant human anti-rabies IgG1
monoclonal antibody) against plasma-derived human rabies immunoglobulin
(HRIG) (Zhang 2022). Output Cc is neutralizing antibody activity in
IU/mL measured by the rapid fluorescent focus inhibition test (RFFIT).
The published Y1 two-compartment PK overlay for the passive-antibody
component of the combined drug+vaccine groups (E = Y1 + Y2) is NOT
included here because the seven structural PK constants (Ka, V1, V2,
K10, K12, K21, C0) are not reported anywhere on disk; see the vignette’s
Assumptions and deviations section for the omitted-component audit
trail.
|
|
Osimertinib
(Brown 2017)
|
Joint two-compartment population PK model for osimertinib (AZD9291) and
its active metabolite AZ5104 in advanced non-small cell lung cancer
(NSCLC) patients pooled with healthy volunteers (Brown 2017).
First-order oral absorption into a parent (osimertinib) compartment is
followed by a second compartment (AZ5104) in series; the fraction of
parent eliminated as AZ5104 is fixed at 0.25 per the publication. Body
weight (allometric on parent CL/F and Vc/F and on AZ5104 CL/F), serum
albumin (power on parent Vc/F), healthy-volunteer disease state (linear
factor on both parent and AZ5104 CL/F), and ethnicity (Chinese,
Japanese, Asian-other, and non-Asian non-Caucasian linear factors on
AZ5104 CL/F) were retained as significant covariates.
|
|
Oxcarbazepine
(Rodrigues 2017)
|
Parent-metabolite population PK model for oral oxcarbazepine (OXC) and
its active monohydroxy derivative (MHD) in epileptic children aged 2-12
years (Rodrigues 2017). Two-compartment OXC + one-compartment MHD with
first-order absorption, complete metabolic conversion (Fm fixed to 1),
reversible MHD-to-OXC back-transformation (KBT), empirical allometric
weight scaling on CL_OXC/F, Vc_OXC/F, CL_MHD/F, and Vc_MHD/F (no scaling
on Q_OXC/F or Vp_OXC/F), and a 29.3% increase in MHD clearance under
concomitant enzyme-inducing antiepileptic drugs.
|
|
Ozoralizumab
(Takeuchi 2023)
|
One-compartment population PK model with first-order absorption for
subcutaneous ozoralizumab (anti-TNF VHH NANOBODY) in Japanese patients
with rheumatoid arthritis (Takeuchi 2023)
|
|
Palivizumab
(Robbie 2012)
|
Two-compartment population PK model for palivizumab (anti-RSV humanized
IgG1 kappa mAb) with first-order IM absorption in adults and children
(Robbie 2012)
|
|
PAmAb
(Cao 2013)
|
Second-generation minimal physiologically-based PK (mPBPK) model for
PAmAb in adults (Cao 2013 Model A; clearance from plasma)
|
|
Paracetamol
(Krekels 2015)
|
Parent-and-metabolites population PK model for intravenous paracetamol
(administered as the prodrug propacetamol; doses expressed as
paracetamol equivalents) and its glucuronide and sulphate phase-II
conjugates in 54 preterm and term neonates and infants (Krekels 2015).
One-compartment plasma disposition for paracetamol with three parallel
elimination pathways from the central compartment: glucuronide formation
(CL_gluc), sulphate formation (CL_sulf), and unchanged renal excretion
(CL_renal). Each metabolite distributes into a one-compartment plasma
space whose volume is fixed at 18% of the parent volume (Vc_gluc =
Vc_sulf = 0.18 * Vc, based on the previously reported adult paracetamol
model in Allegaert et al. and adult literature). The two metabolites
share a common urinary excretion rate constant kE_met = mf * kE_renal,
where kE_renal = CL_renal / Vc is the parent unchanged-renal rate
constant and mf (multiplication factor) is estimated to be 11.3.
Cumulative urinary amounts of parent paracetamol and the two metabolites
are tracked as elimination-amount compartments and exposed as
additive-error observations. Bodyweight enters linearly on Vc (and so on
the metabolite volumes by inheritance), on the glucuronide formation
clearance (CL_gluc), and on the unchanged renal clearance (CL_renal);
the sulphate formation clearance (CL_sulf) scales with bodyweight as a
power with an estimated exponent of 1.40. No postnatal age,
postmenstrual age, sex, term-vs-preterm, or study-protocol covariate was
retained in the final model, and no time-varying (up-regulation)
component was detected on the glucuronidation pathway. Parameter values
reported throughout (mL/min/kg, L/kg) are per-kg quantities; individual
structural parameters are obtained in model() by multiplying by body
weight in kg (linear) or body weight in kg raised to n (power).
|
|
Paroxetine
(Kim 2015)
|
One-compartment population PK model with first-order absorption for
paroxetine (SSRI antidepressant) in Korean adults with major depressive
disorder or anxiety disorder receiving therapeutic drug monitoring (Kim
2015).
|
|
Patritumab
(Lu 2022)
|
Joint two-analyte population PK model for patritumab deruxtecan
(HER3-DXd, an anti-HER3 antibody-drug conjugate) in adults with
HER3-expressing solid tumors (Lu 2022). DXd-conjugated antibody (intact
ADC) is described by a 2-compartment model with parallel linear and
Michaelis-Menten clearance. Released unconjugated DXd (MAAA-1181a,
exatecan-derivative payload) is described by a 1-compartment model with
linear clearance and a first-order, time-dependent release rate driven
by the level of DXd-conjugated antibody in the central compartment,
scaled by the molecular-weight ratio MW_DXd/MW_DXdAb and a
payload-to-intact-drug ratio PIR modulated by a cycle-1-vs-later
(factor1) and a within-cycle exponential (factor2) modifier.
|
|
Pazopanib
(Ouerdani 2015)
|
Semi-mechanistic tumour growth and angiogenesis-inhibition (TGI) model
for pazopanib in renal-cell carcinoma patients (Ouerdani 2015 clinical
fit): logistic tumour growth (state tumorSize) limited by a separately
tracked vasculature-determined carrying capacity (state
carryingCapacity), with antiangiogenic and cytotoxic drug effects
parameterised as power functions of per-period mean AUC_PAZO and an
exponentially declining resistance on the cytotoxic effect. The
empirical exponent on capacity growth (n) is fixed at 0.5 for the
clinical fit (vs 1 in the paired mouse model) to better describe the
tumour-regrowth and long-term-antiangiogenic phases observed in
patients.
|
|
Pazopanib
mouse (Ouerdani 2015)
|
Preclinical (mouse, CB-17 SCID with CAKI-2 renal-cell carcinoma
xenografts). Semi-mechanistic tumour growth and angiogenesis-inhibition
(TGI) model for pazopanib (Ouerdani 2015): logistic tumour growth (state
tumorSize) limited by a separately tracked vasculature-determined
carrying capacity (state carryingCapacity), with an antiangiogenic drug
effect on carrying-capacity loss (power form in AUC_PAZO) and a putative
cytotoxic drug effect on tumour decay (exponentially declining
resistance, no AUC effect after the cytotoxic exponent was fixed to 0).
|
|
Pembrolizumab
(Ahamadi 2017)
|
Two-compartment population PK model for pembrolizumab (humanized
anti-PD-1 IgG4 monoclonal antibody) with allometric scaling and
covariate effects of sex, albumin, tumor type, ECOG performance status,
prior ipilimumab status, eGFR, and baseline tumor burden, in adults with
advanced solid tumors (Ahamadi 2017, KEYNOTE-001/-002/-006)
|
|
Pembrolizumab
(Elassaiss-Schaap 2017)
|
Two-compartment population PK model with parallel linear and
Michaelis-Menten clearance plus a direct-response Imax PK/PD model on
the ex vivo IL-2 stimulation ratio (PD-1 target engagement) for IV
pembrolizumab (anti-PD-1 IgG4 mAb) in adults with advanced solid tumors
(Elassaiss-Schaap 2017, KEYNOTE-001 parts A, A1, A2).
|
|
Pertuzumab
(Garg 2014)
|
Two-compartment population PK model with first-order linear elimination
from the central compartment for intravenous pertuzumab (PERJETA) in
patients with a variety of HER2-targeted solid tumors (Garg 2014)
|
|
Pertuzumab
(Wang 2021)
|
Two-compartment population PK model with first-order subcutaneous
absorption and bioavailability for pertuzumab (Perjeta) administered
either intravenously or as the fixed-dose combination subcutaneous
formulation with trastuzumab (PH FDC SC) in patients with HER2-positive
early breast cancer in the FeDeriCa study (Wang 2021)
|
|
PF
06939999 (Guo 2022)
|
Population PK/PD model for PF-06939999 (a small-molecule PRMT5
inhibitor) in 28 adults with advanced solid tumors enrolled in the
dose-escalation part of NCT03854227. PK is a two-compartment model with
first-order absorption (CL/F, V1/F, Q/F, V2/F, Ka). Plasma SDMA (the PD
biomarker for PRMT5 inhibition) is modelled by an indirect-response
model with saturable Imax inhibition on zero-order SDMA production
(Kin/Kout), the log-transformed SDMA observation taking an additive
(log-normal) residual error. Platelet count is described by the Friberg
semi-mechanistic myelosuppression model (proliferating cells plus three
transit compartments feeding a circulating compartment) with a linear
drug effect Slope*Cc on the proliferation rate and feedback
(Circ0/circ)^gamma.
|
|
Phenytoin
(Hennig 2015)
|
One-compartment population PK model for phenytoin in critically ill
children with a linear partition coefficient describing protein binding
to albumin (Hennig 2015).
|
|
Phenytoin
(Tanaka 2012)
|
Two-compartment population PK model for phenytoin after IV fosphenytoin
sodium administration in Japanese healthy volunteers and adult /
pediatric patients (Tanaka 2012). The fosphenytoin compartment converts
first-order (K12) to the phenytoin central compartment; phenytoin is
cleared from central and exchanges with a peripheral compartment via Q.
|
|
Phenytoin
(Yukawa 1990)
|
Steady-state Michaelis-Menten population PK model for phenytoin in 334
Japanese epilepsy outpatients on chronic oral phenytoin (Yukawa 1990
Model 2). Covariate effects on Vmax (allometric body weight,
co-anticonvulsants) and Km (age <15 yr, co-anticonvulsants);
dose-dependent powder bioavailability.
|
|
Piperacillin
(Boer-Perez 2026)
|
One-compartment population PK model for piperacillin in preterm and term
neonates with severe infections (Boer-Perez 2026); body-weight
allometric scaling, sigmoidal postmenstrual-age maturation on CL fixed
from Rhodin 2009, and a power effect of serum creatinine on CL.
|
|
Polatuzumab
(Lu 2019)
|
Integrated two-analyte population PK model of polatuzumab vedotin
(anti-CD79b vc-MMAE antibody-drug conjugate) in adults with non-Hodgkin
lymphoma (Lu 2019). The antibody-conjugated MMAE (acMMAE) is described
by a two-compartment model with three parallel elimination pathways from
the central compartment: a slowly-time-decaying nonspecific linear
clearance (CL_NS, sigmoidal Hill decline with cycle), a rapidly-decaying
linear clearance (CL_t, mono-exponential decline), and a saturable
Michaelis-Menten clearance (CL_MM). All three acMMAE pathways feed
unconjugated MMAE formation in the central MMAE compartment with
relative conversion fractions FRAC_NS, FRAC_NS x FRAC_CLT, and FRAC_NS x
FRAC_MM, modulated by a time-dependent multiplier (1 + FRAC_T x
exp(-alpha x t)) on FRAC_NS that captures the cycle-over-cycle decline
in MMAE formation. Unconjugated MMAE is described by an apparent
two-compartment model with parallel linear (CL_MMAE) and
Michaelis-Menten (Vmax_MMAE / KSS) elimination from its central
compartment. Modeled in MMAE-equivalent micrograms (pola dose in ug/kg x
weight in kg x 3.65 x 718 / 145001 -> MMAE-equivalent ug administered
to the acMMAE central compartment), with concentrations in ng/mL = ug/L.
The Asian-race indicator on acMMAE Vc (e_asian_vc = 0.929, i.e., 7.1%
lower V1 in Asian patients) is retained from the Lu 2019 final model and
was subsequently re-quoted and assessed as not clinically meaningful in
the Shi 2020 ethnicity-sensitivity analysis (PMID 32770353) of the same
upstream popPK model.
|
|
Posdinemab
(PerezRuixo 2025)
|
Mechanism-based population PK-PD model with full TMDD for the anti-tau
monoclonal antibody posdinemab in serum, CSF, and ISF (Perez-Ruixo
2025): two-compartment serum disposition with linear elimination,
distribution into a CSF compartment and a downstream ISF compartment,
explicit second-order binding of free posdinemab to free p217+tau in CSF
and to tau seeds in ISF, internalization of free target and drug-target
complex, and Alzheimer’s-disease-vs-healthy effect on baseline p217+tau.
|
|
Pozelimab
(Lin 2024)
|
Two-compartment two-binding-site TMDD-QE population PK model of total
pozelimab and total C5 in healthy volunteers, adults with paroxysmal
nocturnal hemoglobinuria, and pediatric and adult patients with CHAPLE
disease (Lin 2024)
|
|
Pravastatin
(Ide 2009)
|
Population PK model for orally administered pravastatin with
enterohepatic circulation (Ide 2009) in healthy Japanese male
volunteers. Absorption is described by an Erlang chain of 8 transit
compartments (N_depot = 8); disposition is one-compartment central with
a gallbladder recirculation compartment whose release is gated by the
gallbladder-emptying time tg (continuous filling from central via k12
for t < tg, gated release to central via k21 for t >= tg)
producing the characteristic second-peak phenomenon. SLCO1B1 *15
haplotype carrier status (paired heterozygote / homozygote indicators)
increases relative oral bioavailability Frel multiplicatively (1.50x and
1.95x respectively). Gastric conversion of pravastatin to its inactive
3’alpha-isopravastatin (RMS-416) is highly variable; the source paper
corrected for this by using an apparent dose (actual dose x Fa, where Fa
= AUCpra / (AUCpra + AUCrms)) as the model input, so the packaged model
fixes the depot bioavailability anchor at the population-mean Fa = 0.571
derived from Table II mean AUC values.
|
|
PRO95780
(Cao 2013)
|
Second-generation minimal physiologically-based PK (mPBPK) model for
PRO95780 (drozitumab) in adults (Cao 2013 Model A; clearance from
plasma)
|
|
Propofol
(Diepstraten 2013)
|
Three-compartment intravenous population PK model for propofol in
morbidly obese and nonobese adults, adolescents, and children
(Diepstraten 2013 meta-analysis of five previously published studies; N
= 94 patients, TBW 37-184 kg, age 9-79 years). Final model E in Table 3:
total body weight scales clearance allometrically with an estimated
exponent and scales the slow inter-compartmental clearance Q3 linearly;
age modifies clearance via a bilinear function centered at 41 years with
separate slopes below and above the breakpoint. Inter-individual
variability on CL, V1, V3, and Q3 (log-normal) and proportional
intra-individual error on log-transformed concentrations.
|
|
Pyrazinamide
(Alsultan 2017)
|
One-compartment population pharmacokinetic model with first-order
absorption and first-order elimination for oral pyrazinamide in adults
with drug-susceptible pulmonary tuberculosis (Alsultan 2017); body
weight is an allometric covariate on CL/F and V/F (fixed exponents 0.75
and 1) and biological sex is an exponential covariate on V/F
|
|
Quinine
rat (Sheng 2016)
|
Preclinical (rat). Two generalized Poisson (2GP) mixture PD model for
bimodal lick-count data from rodent brief-access taste aversion (BATA)
experiments with quinine hydrochloride dihydrate; the drug effect enters
via a sigmoid Emax on a logistic-transformed mixing probability between
a low-count and a right-truncated high-count generalized-Poisson
distribution. The fitted compound is quinine HCl dihydrate used as a
model bitter stimulus. STIM_QUININE_MM is the applied sipper-tube
concentration (mM); there is no PK ODE and no time evolution (each
record is an 8-second presentation).
|
|
Ranibizumab
(Mulyukov 2018)
|
Indirect-response PK/PD model of intravitreal ranibizumab on
best-corrected visual acuity (BCVA, ETDRS letters) in anti-VEGF-naive
adults with neovascular age-related macular degeneration (Mulyukov
2018). BCVA is driven by an indirect-response ODE in which drug
concentration stimulates the BCVA production rate (kin) through a
Michaelis-Menten-like term with a time-dependent maximum effect Emax(t)
= Emax_ss + dEmax_0 * exp(-kEmax * t). The PK is a fixed first-order
vitreous-elimination placeholder (kel = 0.077/day, vitreous volume = 4
mL, no IIV) borrowed from a previous population PK analysis (reference
20 of the paper) because vitreous PK data were not collected in the
development studies.
|
|
RFIXFc
(Diao 2014)
|
Three-compartment population PK model for recombinant factor IX Fc
fusion protein (rFIXFc, eftrenonacog alfa) in patients with severe to
moderate haemophilia B aged 12-77 years (Diao 2014). Disposition is
described by linear three-compartment kinetics with intravenous input
and first-order elimination from the central compartment; body weight is
the only retained covariate, scaling CL and V1 with estimated power
exponents (not the canonical 0.75 / 1) and a reference weight of 73 kg.
|
|
Rifabutin
(Hennig 2015)
|
Two-compartment population pharmacokinetic model for rifabutin with
simultaneous two-compartment metabolite (25-O-desacetyl rifabutin)
modelling in 44 African HIV-infected adults with pulmonary tuberculosis
on 300 mg daily oral rifabutin (Hennig 2015). Body weight allometrically
scaled (a priori; CL exponent 0.75, V exponent 1) on all rifabutin
apparent clearances and apparent volumes; sex effect on rifabutin V/F
(males 1.84-fold higher than females); SLCO1B1 rs11045819
heterozygous-AC genotype increases rifabutin bioavailability F by 30.4
percent relative to homozygous-CC reference. Des-rifabutin parameters
are apparent (with respect to rifabutin F and metabolite-formation
fraction) and were estimated without allometric scaling, with metabolite
Q and peripheral V fixed.
|
|
Rifampicin
(Clewe 2015)
|
Pharmacometric pulmonary distribution model for rifampicin in adults
without tuberculosis: a one-compartment plasma PK model with
single-transit oral absorption coupled to a Smythe 2012 enzyme-pool
autoinduction structure (MTT, N, EMAX, EC50, kENZ all fixed from the
upstream Smythe 2012 model) plus two effect compartments capturing
distribution from plasma to epithelial lining fluid (ELF) and alveolar
cells (AC); CL/F and Vc/F are FFM-allometrically scaled to 70 kg, the
ELF and AC equilibration rate constants kELF and kAC are fixed to an
equivalent 1-min half-life (instantaneous distribution at the single 4-h
post-dose BAL sampling time), and only the unbound steady-state
ELF/plasma and AC/plasma concentration ratios are estimated (1.28 and
5.5 after correction for the 20% rifampicin plasma free fraction).
|
|
Rifampicin
(Svensson 2016)
|
Combined population PK/PD model for rifampicin in adults with
drug-susceptible pulmonary tuberculosis: a one-compartment,
single-transit, oral PK model with first-order
plasma-concentration-driven autoinduction of clearance via an
enzyme-pool turnover (structure from Smythe 2012) linked to the
Multistate Tuberculosis Pharmacometric (MTP) three-state bacterial
disease model (fast-, slow-, and nonmultiplying Mycobacterium
tuberculosis states; structure from Clewe 2016) with rifampicin drug
effects as fixed-at-100% on/off inhibition of fast-multiplying bacterial
growth plus second-order plasma-concentration-driven death of slow- and
nonmultiplying bacteria; all PK parameters and all MTP transfer/growth
rates are fixed to the upstream-paper estimates, while the system
carrying capacity Bmax (with 152% CV IIV) and the two second-order death
rates SDk and NDk are re-estimated against 19 patients from a 1966-1977
Kenyan rifampicin monotherapy trial.
|
|
Rilotumumab
(Zhang 2016)
|
Two-compartment IV population PK model for rilotumumab (fully human
anti-HGF IgG2 monoclonal antibody) in patients with MET-positive gastric
or gastroesophageal-junction adenocarcinoma receiving rilotumumab in
combination with epirubicin / cisplatin / capecitabine (ECX). The
structural model and parameter values were inherited from the previously
developed population PK analysis of rilotumumab (Zhu et al. 2014, J
Pharm Sci 103:328-336); Zhang 2016 reports the typical-value point
estimates and IIV %CV from that prior model and uses it as the reference
for an external visual predictive check assessing whether ECX
co-administration alters rilotumumab PK.
|
|
Risankizumab
(Suleiman 2019)
|
Two-compartment population PK model of risankizumab (anti-IL-23 mAb)
with first-order SC absorption in healthy subjects and patients with
moderate-to-severe plaque psoriasis (Suleiman 2019)
|
|
Risankizumab
(Thakre 2022)
|
Two-compartment population PK model of risankizumab (anti-IL-23 mAb)
with first-order SC absorption in patients with active psoriatic
arthritis (Thakre 2022)
|
|
Rivipansel
(Tammara 2017)
|
Three-compartment IV population PK model for rivipansel in adults and
adolescents with sickle cell disease (SCD) and in healthy adult
volunteers (Tammara 2017). Rivipansel is a pan-selectin antagonist given
as a 20-minute IV infusion; renal excretion of unchanged drug is the
primary clearance mechanism. The integrated population PK model pools
109 subjects across three phase I studies (rivipansel studies 101, 102,
103) and one phase II SCD study (NCT01119833, Telen 2015). Clearance is
a power function of creatinine clearance (CRCL, raw Cockcroft-Gault
mL/min reference 150) with an additive 23.4% shift in the phase II SCD
cohort (STUDY_RIV201) attributed to glomerular hyperfiltration. The
central, first peripheral, and second peripheral volumes share a single
estimated body-weight exponent (0.569, reference 70 kg). The additive
and proportional residual error magnitudes differ between the phase I
and phase II cohorts and are selected per observation via STUDY_RIV201.
|
|
Rocatinlimab
(Okada 2025)
|
Two-compartment population PK model with parallel linear and
time-dependent saturable (Michaelis-Menten) clearance and first-order
subcutaneous absorption for rocatinlimab (anti-OX40 mAb) in adults;
covariates body weight, albumin, plaque-psoriasis disease state, and
healthy-volunteer cohort indicator (Okada 2025)
|
|
Roflumilast
(Lahu 2010)
|
Joint parent-metabolite population PK model for oral roflumilast and its
primary active metabolite roflumilast N-oxide in adult healthy
volunteers and patients with moderate-to-severe COPD (Lahu 2010).
Roflumilast is described by a two-compartment model with first-order
absorption and a lag time; the absolute parent bioavailability is not
identifiable and is fixed at F1 = 1. Roflumilast N-oxide is described by
a one-compartment model with zero-order absorption (duration D1) and a
lag time, with relative bioavailability Frel fixed at 1 for the
null-covariate reference (also non-identifiable). Retained covariates on
roflumilast parameters are food on tlag and ka, sex / smoking /
race-Black / race-Hispanic / COPD on CL, and COPD on V1. Retained
covariates on roflumilast N-oxide parameters are food on D1; age / sex /
smoking / COPD on CL; body weight and COPD on Vd; and age / sex /
race-Black / race-Hispanic on Frel. Inter-individual variability is
reported on parent tlag, ka, CL, V1, Q, V2 (with a Q-V2 covariance) and
on N-oxide D1, CL, Vd (with a full 3x3 covariance block); no IIV is
reported on N-oxide tlag or on Frel. Residual error is proportional on
the linear- concentration scale (additive on the log-transformed
observation) for both observed analytes, fitted on the phase I dataset
(the more data-rich layer).
|
|
Romiplostim
(Petrov 2024)
|
Population PK/PD model for romiplostim in adults with chronic immune
thrombocytopenia (ITP). One-compartment first-order subcutaneous PK plus
an Emax stimulation of platelet precursor production into a
4-transit-compartment Friberg-style chain feeding circulating platelets,
with first-order platelet degradation. PK/PD backbone is the
healthy-volunteer population PK/PD model (Makarenko 2024); ITP-specific
platelet production (kin) and degradation (kdeg) constants and IIV(kdeg)
come from Petrov 2024 supplement Table S1. Default parameters are
non-splenectomized ITP patients with mechanism 1 (increased platelet
degradation, normal precursor production); see vignette for the other 3
subpopulation variants (non-splenectomized mechanism 2; splenectomized
mechanism 1; splenectomized mechanism 2).
|
|
Rosuvastatin
(Macpherson 2015)
|
Two-compartment population PK model with first-order oral absorption for
rosuvastatin in pediatric patients (aged 6 to <18 years) with
heterozygous familial hypercholesterolemia (Macpherson 2015 Eur J Clin
Pharmacol). Apparent clearance scales with body weight (estimated power
exponent 0.352, reference 42 kg) and is 1.41-fold higher in males than
females. Residual error is proportional and switches between intensive
and sparse PK sampling phases.
|
|
Rucaparib
(Wang 2015)
|
Three-compartment IV population PK model coupled to a direct-effect Emax
PK/PD model for inhibition of poly(ADP-ribose) polymerase (PARP-1)
activity in peripheral blood lymphocytes (PBL) by rucaparib (AG-014699 /
PF-01367338) in adult cancer patients (Wang 2015 Phase 1 study
A4991002), with a power covariate effect of baseline PBL PARP activity
on the residual maximum-inhibition parameter Emin.
|
|
Sacituzumab
(Sathe 2024)
|
Coupled three-analyte population PK model for sacituzumab govitecan (SG,
the ADC; output Cc), free SN-38 (released payload; output Cc_sn38), and
total antibody (tAB; output Cc_tab) in adults with metastatic
triple-negative breast cancer and other solid tumors (Sathe 2024). All
three analytes are described by two-compartment models with body-weight
allometric scaling. SG carries IIV on CL and a baseline-albumin power
covariate on CL. Free SN-38 is generated from SG by a first-order
release rate KREL with apparent volumes fixed to literature values
(Klein 2002). tAB has time-dependent CL (asymptotic onset, max ~17%
reduction at t1/2 ~48 days), correlated IIV on CL and V1, and covariates
of baseline albumin (CL), tumor type (CL), and sex (V1). Simulation
requires dosing two compartments simultaneously (central and
central_tab) for each SG infusion event.
|
|
SAL003
(Peng 2024)
|
Two-compartment population PK model for SAL003, a novel anti-PCSK9 IgG4
monoclonal antibody, with first-order SC absorption (with lag time),
saturable Michaelis-Menten elimination from the central compartment, and
a body-weight effect on central volume, in Chinese healthy volunteers
and patients with hyperlipidemia (Peng 2024)
|
|
Sapropterin
(Qi 2014)
|
One-compartment population PK model with first-order oral absorption, an
absorption lag, linear elimination, and an additive endogenous BH4
baseline for sapropterin dihydrochloride in pediatric and adult patients
with phenylketonuria (Qi 2014).
|
|
Sarilumab
(Xu 2019)
|
Two-compartment population PK model for sarilumab in adults with
rheumatoid arthritis (Xu 2019), with first-order SC absorption and
parallel linear plus Michaelis-Menten (target-mediated) elimination from
the central compartment.
|
|
Sarilumab
anc (Ma 2020)
|
Indirect-response PopPK/PD model for absolute neutrophil count (ANC)
following subcutaneous sarilumab in adults with rheumatoid arthritis (Ma
2020). Sarilumab concentrations drive stimulation of ANC elimination
(margination); PK backbone is Xu 2019.
|
|
Sarilumab
das28crp (Ma 2020)
|
Indirect-response PK/PD model of sarilumab on the 28-joint disease
activity score by C-reactive protein (DAS28-CRP) in adults with
rheumatoid arthritis (Ma 2020). Sarilumab inhibits the DAS28-CRP
production rate (kin) via a sigmoid Emax function that includes a
background DMARD placebo component (PLB). The PK driver is the
two-compartment, parallel linear + Michaelis-Menten model of Xu 2019
evaluated at its typical covariate-reference values (adult female, 71
kg, ADA-negative, commercial drug product, ALBR = 0.78, CrCl = 100
mL/min/1.73 m^2, baseline CRP = 14.2 mg/L).
|
|
Selexipag
(Krause 2017)
|
Joint two-compartment parent + two-compartment metabolite population PK
model for oral selexipag and its active metabolite ACT-333679 in adults
with pulmonary arterial hypertension (Krause 2017, GRIPHON study).
First-order absorption with a fixed 0.668 h absorption lag delivers
selexipag into a two-compartment disposition with linear total clearance
CL/F (apparent total clearance, of which the rate constant kmet
describes the fraction converted to ACT-333679); the metabolite has its
own two-compartment disposition with first-order elimination via km.
Body weight (allometric on V_p/F and CL/F; on V_m/F), total bilirubin
(power on CL/F), sex (multiplicative on km), and a four-level
PAH-comedication categorical (naive / ERA only / PDE5 inhibitor only /
ERA + PDE5 combined; multiplicative on km) were retained as
statistically significant covariates.
|
|
Selumetinib
(Patel 2017)
|
Sequential two-compartment population PK model for oral selumetinib
(AZD6244, ARRY-142886) and its active metabolite N-desmethyl-selumetinib
in adults with advanced solid tumors pooled with children with recurrent
low-grade glioma (Patel 2017). Selumetinib disposition uses sequential
zero-order (release into the gut compartment over duration D1 with lag
ALAG1) and first-order (rate Ka) absorption with bioavailability
anchored at 1 under fasted conditions and reduced by an additive
food-effect coefficient under fed conditions; D1 and ALAG1 carry
additive food-effect coefficients. Body surface area (power on CL/F and
Vc/F), age (power on Vc/F), and alanine aminotransferase (negative power
on CL/F) modify selumetinib parameters; BSA (negative power) modifies
the fraction metabolized to N-desmethyl-selumetinib. The metabolite is
two-compartment with its central volume fixed equal to the parent
central volume to resolve identifiability; metabolite clearance and
intercompartmental clearance are apparent values.
|
|
Semaglutide
(Overgaard 2019)
|
Two-compartment population PK model for subcutaneous semaglutide (GLP-1
receptor agonist) with first-order absorption and first-order
elimination, pooled across nine clinical pharmacology trials in healthy
volunteers and adults with type 2 diabetes (Overgaard 2019).
|
|
Sibutramine
(Han 2015)
|
Two-compartment population PK for the active mono-desmethyl metabolite
M1 plus a one-compartment PK for the downstream di-desmethyl metabolite
M2 of the appetite-suppressant prodrug sibutramine, combined with an
asymptotic exposure-response weight-loss PD model in Korean obese adults
with metabolic syndrome. Sibutramine is dosed orally and assumed to
convert entirely to M1 during absorption; M1 is then metabolised
entirely to M2 and M2 is the only elimination pathway. Drug effect
inhibits the rate of weight gain via a sigmoid Emax function of the
steady-state sum AUC of M1 and M2 (AUC_ss,sum, computed from the current
daily dose and the individual M1 and M2 clearances). A constant placebo
effect is acknowledged only in female subjects and scales with
mean-normalised baseline BMI.
|
|
Sifalimumab
(Narwal 2013)
|
Two-compartment population PK model for sifalimumab (anti-IFN-alpha
IgG1) in adult patients with systemic lupus erythematosus (Narwal 2013)
|
|
Sifalimumab
(Zheng 2016)
|
Two-compartment population PK model for sifalimumab (anti-IFN-alpha
human IgG1 monoclonal antibody) in adults with systemic lupus
erythematosus following repeat fixed intravenous doses (Zheng 2016).
|
|
Siltuximab
(Cao 2013)
|
Second-generation minimal physiologically-based PK (mPBPK) model for
siltuximab in adults (Cao 2013 Model A; clearance from plasma)
|
|
Siltuximab
(Nikanjam 2019)
|
Two-compartment population PK model for siltuximab (anti-IL-6) in adults
pooled across healthy volunteers and oncology cohorts including
Castleman’s disease, smoldering multiple myeloma, and other tumor types
(Nikanjam 2019)
|
|
Simvastatin
(Jin 2014)
|
Joint two-compartment population PK model for orally administered
simvastatin (lactone parent) and its active metabolite simvastatin acid
(open beta-hydroxyacid), describing atypical multiple-peak absorption
via three parallel mixed zero-and-first-order absorption processes and
non-equilibrium reversible interconversion between the two species (Jin
2014). The simvastatin lactone is delivered into three depot
compartments with fractional bioavailabilities F1, F2, F3 (sum = 1)
parameterised through two relative-bioavailability constants BA1 and
BA2, each depot has its own first-order absorption rate constant Ka1,
Ka2, Ka3, zero-order infusion duration D1, D2, D3, and absorption
lag-times ALAG1 = 0, ALAG2, ALAG3, the lactone disposes via a
2-compartment system with apparent clearance CL and inter-compartmental
clearance Q, the fraction FM of total parent CL is converted to
simvastatin acid (V_acid central fixed at 1 L for identifiability), and
a reverse clearance Q64 returns acid to the parent central compartment.
Age, body weight, and height were tested as covariates and not retained
in the final model. The source publication analysed data in molar units;
this packaged model preserves that choice – doses are expressed in nmol
and concentrations in nmol/L. The validation vignette demonstrates the
standard milligram-to-nanomole conversion using the simvastatin lactone
molecular weight.
|
|
Sirolimus
(Wu 2012)
|
Two-compartment population PK model for oral sirolimus with saturable
Michaelis-Menten absorption in patients with advanced cancer (Wu 2012).
Hematocrit power covariate on apparent oral clearance.
|
|
Sirukumab
(Xu 2011)
|
Two-compartment population PK model for sirukumab (anti-IL-6 human IgG1
kappa monoclonal antibody, CNTO 136) in healthy adults following a
single intravenous infusion, with first-order elimination from the
central compartment and allometric body-weight scaling (Xu 2011).
|
|
Sodium
nitrite qsp (VegaVilla 2013)
|
QSP. Mechanistic systems pharmacology model of the NO metabolome
(nitrite, nitrate) and methemoglobin (MetHb) in healthy adults receiving
a 48-hour intravenous infusion of sodium nitrite. Nine ODEs covering
plasma/RBC/tissue nitrite and nitrate, MetHb, NO and methemoglobin
reductase activity; nonlinear nitrite/nitrate renal clearance (linear
slope), entero-salivary nitrate-to-nitrite recycling, and
indirect-response stimulation of MetHb reductase. Time in minutes;
amounts in umol; concentrations in umol/L.
|
|
Somatropin
human (Thorsted 2016)
|
Translational (allometrically-scaled rat-to-human) population PKPD model
for recombinant human growth hormone (rhGH / somatropin) in
growth-hormone-deficient adult males. Structural parameter values are
derived from the Thorsted 2016 hypophysectomized-rat PKPD fit by
allometric scaling to a 70 kg reference subject (Table 3 of the source
paper): clearance terms (CL, Q) and Vmax with exponent 0.75;
distribution volumes (Vc, Vp) with exponent 0.9 (the
empirically-selected best-fit exponent for human i.v. data); first-order
absorption rate constants (ka1, ka2) and kout with exponent -0.25; KM
unscaled; Emax and EC50 unscaled. The s.c. absorption model is the
corrected form (Table 3 / Figure 5): bioavailability of the ka2 path
reduced from 0.833 (rat) to 0.500, and one transit compartment added to
the ka1 path. The IGF-1 indirect response uses kin = kout * R0 with R0
fixed to 65 ng/mL (human population mean per Laursen 1996) and is driven
directly by plasma rhGH (no effect-delay chain - the rat CPLAG chain is
intentionally dropped for the human prediction). Bodyweight gain is not
included in the human model. Variability is inherited from the rat PKPD
fit; residual error is fixed at the values used for the human-simulation
validation (Methods).
|
|
Somatropin
rat (Thorsted 2016)
|
Preclinical (hypophysectomized Sprague-Dawley rat). Mixed-effects PKPD
model for recombinant human growth hormone (rhGH / somatropin)
describing PK as a two-compartment model with parallel linear (CL) and
Michaelis-Menten (Vmax, KM) elimination, parallel first-order
subcutaneous absorption (ka1 direct path, ka2 delayed through one
transit compartment, with bioavailabilities F1 and F2), an indirect
response model for IGF-1 induction (stimulation of kin via a
three-compartment effect-delay chain feeding an Emax/EC50 stimulation),
and a linear bodyweight-gain model driven by IGF-1 above baseline.
Reference rat body weight is 0.1 kg (100 g) and the allometric exponents
(0.75 / 1.0) are fixed.
|
|
Sonidegib
(Goel 2016)
|
Two-compartment population PK model for sonidegib (LDE225) in healthy
subjects and patients with advanced solid tumors with first-order
absorption, lag time, linear elimination, and dose-dependent
bioavailability (Goel 2016)
|
|
Sugemalimab
(Wang 2024)
|
Two-compartment population PK model with sigmoidal-Emax time-varying
clearance for intravenous sugemalimab (anti-PD-L1 IgG4) in adults with
advanced solid tumours or lymphomas across nine Phase I-III trials (Wang
2024)
|
|
SulfadoxinePyrimethamine
(deKock 2017)
|
Joint popPK model for the antimalarial fixed-dose combination of
sulfadoxine (1500 mg) and pyrimethamine (75 mg) as intermittent
preventive treatment during pregnancy (IPTp) and after delivery in 98
women from Mali, Mozambique, Sudan, and Zambia (de Kock 2017).
Sulfadoxine has 2-compartment disposition with first-order absorption;
pyrimethamine has 3-compartment disposition with first-order absorption.
Apparent volumes and flow rates are allometrically scaled with total
body weight (exponents 1 and 0.75 respectively, reference WT = 60 kg).
Whole-blood predictions are derived from plasma predictions using
hematocrit and an estimated RBC-to-plasma partition ratio per drug.
Pregnancy effects on apparent CL differ by drug: sulfadoxine uses a
sigmoidal time-after-delivery effect (asymptotic -75.7%, T50 = 6.35
weeks, gamma = 4.90), while pyrimethamine uses a step contrast (+21.2%
postpartum). Pyrimethamine apparent CL is additionally -20.2% in the
Mozambique site. Residual country-specific scaling on the observed
whole-blood concentrations is fitted with Mali as the reference.
|
|
SulfadoxinePyrimethamine
(Odongo 2015)
|
Joint popPK model for the antimalarial fixed-dose combination of
sulfadoxine (1500 mg) and pyrimethamine (75 mg) administered as a single
oral dose for intermittent preventive treatment of malaria during
pregnancy (IPTp) in 34 non-pregnant and 87 pregnant Ugandan women dosed
in the second trimester, of whom 78 were redosed in the third trimester
(Odongo 2015). Each drug is described by a two-compartment model with
first-order absorption and an absorption lag time, with bioavailability
fixed at 1. Covariates on apparent CL/F (additive in L/h): pregnancy
status (both drugs), serum albumin (sulfadoxine only), and subject age
(pyrimethamine only). Covariates on apparent central volume V2/F
(exponential per-unit): gestational age at dose (both drugs) and body
weight (pyrimethamine only). Inter-individual variability is log-normal
and is not estimated on V2/F or V3/F for sulfadoxine, nor on Q/F for
pyrimethamine, in line with the paper’s over-parameterisation control.
|
|
Sunitinib
(Ait-Oudhia 2016)
|
Joint population PK/PD model for sunitinib and its equipotent active
metabolite SU12662 in adults with advanced hepatocellular carcinoma
(HCC) receiving 37.5 mg sunitinib PO QD. Parent drug and metabolite each
follow a 2-compartment oral PK structure with first-order absorption;
each oral sunitinib dose deposits Dose into the parent depot and fM *
Dose (fM = 0.21 fixed, Houk 2009) into the SU12662 depot. The active
free (unbound) drug concentration ACub = (1 - fb_D) * Cc + (1 - fb_M) *
Cc_su12662 (fb_D = 0.9, fb_M = 0.95 fixed, free fractions 0.1 and 0.05)
inhibits the zero-order production rate of plasma sVEGFR2, captured with
an indirect-response model dsVEGFR2/dt = kin / (1 + alpha * INH) - kout
* sVEGFR2 with INH = ACub / (kd + ACub) (kd = 4 ug/L fixed, Mendel 2003)
and kin = R0 * kout. Tumor volume follows a first-order growth dTG/dt =
kg * (1 - H(t)) * TG with kg derived from baseline tumor volume by kg =
ln(2) / (114 * TG0^0.14) (Taouli 2005) and H(t) = Imax * dsVEGFR2 /
(dsVEGFR2 + dIC50) with Imax = 1 fixed and dsVEGFR2 = R0 - sVEGFR2(t).
The paper reports a significant covariate effect of the DCE-MRI
volume-transfer constant Ktrans on dIC50 (power coefficient 2.12) but
the cohort-median Ktrans required to centre that effect is not reported
in the paper or supplements on disk; the effect is omitted from model()
and documented in the vignette. A Cox-style time-to-tumor progression
hazard h(t) = b0 * exp(b1 * dAUC24h_sVEGFR2) is described in the paper
but evaluated post-simulation in the vignette, not encoded as an ODE.
|
|
Sunitinib
irinotecan mouse (Wilson 2015)
|
Preclinical (mouse with HT-29 colorectal-cancer xenograft). Mechanistic
tumor-growth PD model for the antiangiogenic agent sunitinib (reduces
vascular carrying capacity) combined with the cytotoxic agent irinotecan
(three-stage transit-cell-death chain following Simeoni et al. 2004) and
an empirical interaction term (Wilson 2015 Equation 4) in which the
irinotecan transit-death rate kC depends on the cumulative
pre-irinotecan sunitinib exposure. Drug input is K-PD (no
pharmacokinetic data; each oral sunitinib or 5-min IV irinotecan dose
enters its drug-amount compartment with normalized magnitude 1).
|
|
Tacrolimus
(Benkali 2010)
|
Two-compartment population PK model with Erlang-distributed transit
absorption (3 transit compartments) for once-daily extended-release oral
tacrolimus (Advagraf) in stable adult renal transplant recipients more
than 6 months post-transplant who were switched from twice-daily
ciclosporin (Benkali 2010), with a multiplicative CYP3A5*1-carrier
(expresser) effect on apparent clearance and combined additive +
proportional residual error.
|
|
Tacrolimus
(Bergmann 2014)
|
Two-compartment population PK model for oral tacrolimus in adult kidney
transplant recipients (Bergmann 2014), with first-order absorption after
a lag time, allometric (WT/70 kg)^0.75 scaling on apparent clearance,
multiplicative CYP3A5*1-carrier effect on CL/F, linear hematocrit and
post-transplant-day effects on CL/F, linear free prednisolone Cmax
effect on V1/F, correlated inter-individual variability across V1/F, ka,
and V2/F, and proportional residual error.
|
|
Tacrolimus
(Brooks 2021)
|
Two-compartment population pharmacokinetic model for IV
continuous-infusion tacrolimus in pediatric and young adult patients
undergoing allogeneic hematopoietic cell transplantation (Brooks 2021).
Allometric weight scaling on all PK parameters with fixed theoretic
exponents (0.75 on CL and Q, 1.0 on V and V2; reference weight 70 kg); a
structural ratio Fact fixed at 2.0 links Q to CL and V2 to V; and a
multiplicative azole-antifungal (voriconazole or posaconazole) factor of
0.8 on CL captures the CYP3A4/5 inhibitor co-treatment effect.
|
|
Tacrolimus
(Dunlap 2025)
|
Two-compartment population pharmacokinetic model for oral
immediate-release tacrolimus in adult allogeneic hematopoietic cell
transplant (allo-HCT) recipients (Dunlap 2025): first-order absorption
with bioavailability fixed at 1; allometric (TBW/70 kg) scaling fixed at
0.75 on CL/F and Q/F and at 1 on V1/F and V2/F; exponential CYP3A5
intermediate / normal metabolizer phenotype effect on CL/F (CYP3A5 IM or
NM have ~2.14-fold higher CL/F than CYP3A5 PM); exponential
reduced-intensity-conditioning effect on CL/F (RIC recipients have ~37%
lower CL/F than myeloablative-conditioning recipients); inter-individual
variability on V1/F, CL/F, and V2/F; and an additive residual error of
2.51 ng/mL on the linear concentration scale.
|
|
Tacrolimus
(Kirubakaran 2022)
|
Two-compartment population pharmacokinetic model for oral
immediate-release tacrolimus (Prograf) in adult heart transplant
recipients (Kirubakaran 2022): first-order absorption; FFM-allometric
scaling on CL/F and Q/F (exponent 0.75) and on V2/F and V3/F (exponent
1.0); haematocrit power effect on CL/F; and a state-dependent typical
CL/F (without vs with concomitant azole antifungal, 21.1 vs 4.2 L/h)
with a state-dependent CL/F BSV magnitude (61% vs 89.5% CV). Structural
PK was estimated with NONMEM PRIOR (NWPRI) support from the published
Sikma 2017 thoracic-transplant tacrolimus popPK model.
|
|
Tacrolimus
(Prytula 2016)
|
Two-compartment population PK model with first-order absorption and a
fixed absorption lag time for twice-daily oral tacrolimus (Prograft) in
stable paediatric renal transplant recipients at least one year after
kidney transplantation (Prytula 2016). All apparent-PK parameters (CL/F,
Q/F, V1/F, V2/F, ka) scale allometrically with body weight at fixed
exponents (0.75 on CL/F and Q/F, 1 on V1/F and V2/F, -0.25 on ka)
referenced to a 70 kg adult; V2/F is fixed at 1090 L/70 kg during
covariate analysis; CL/F additionally varies with CYP3A51 carrier
status (1+0.45-fold higher in carriers vs 3/3 nonexpressers),
gamma-glutamyltransferase (power -0.21, centred at 13 U/L), and
haematocrit (power -0.59, centred at 0.34); eta_Q is perfectly
correlated with eta_CL and is constructed as iiv_q_scale etalcl
(iiv_q_scale = 2.0; the ‘IIV-CL-Q’ parameter in Table 2);
inter-individual variability is a 3x3 correlated block on (ka, CL/F,
V1/F); proportional residual error.
|
|
Tacrolimus
(Storset 2014)
|
Theory-based two-compartment population pharmacokinetic model for oral
tacrolimus in adult kidney-transplant recipients (Storset 2014):
plasma-based disposition with first-order absorption and a lag time,
allometric scaling on fat-free mass, CYP3A5-expresser effects on plasma
clearance and oral bioavailability, a sigmoid-Emax prednisolone-driven
reduction in bioavailability, a first-day-post-transplant
bioavailability spike with subject-level random effect, and a saturable
haematocrit-dependent red-blood-cell-binding equation that maps plasma
concentration to whole-blood concentration.
|
|
Tacrolimus
(Woillard 2011)
|
Two-compartment population PK model with Erlang-distributed transit
absorption (3 transit compartments) for oral tacrolimus in adult renal
transplant recipients pooled across the twice-daily immediate-release
Prograf formulation and the once-daily prolonged-release Advagraf
formulation (Woillard 2011), with multiplicative CYP3A5*1-carrier
(expresser) and power-scaled haematocrit effects on apparent clearance,
multiplicative formulation effects on the Erlang transit rate constant
and on apparent central volume, and combined additive plus proportional
residual error.
|
|
Tacrolimus
(Zhu 2014)
|
Two-compartment population PK model for oral tacrolimus in Chinese adult
liver transplant recipients (Zhu 2014), with first-order absorption, a
power-form joint DOSE x POD covariate effect on apparent clearance,
log-normal IIV on CL/F, V2/F, Q/F, V3/F, and ka, and proportional
residual error. Bioavailability was not estimated; the structural
disposition parameters are apparent values (CL/F, V/F, Q/F).
|
|
Tacrolimus
industry meta (Lu 2019)
|
Industry meta-analysis. Two-compartment population PK model for oral
tacrolimus immediate-release (IR-T; Prograf, twice daily) and
prolonged-release (PR-T; Advagraf / Astagraf XL, once daily)
formulations in adult and paediatric liver, kidney, and heart transplant
recipients (Lu 2019). Pooled individual-patient data from 8 Astellas
Phase II studies (n = 408 patients, 23,176 whole-blood concentration
records). Structural model: first-order absorption with
formulation-dependent Ka (PR-T ~50% slower than IR-T), fixed absorption
lag time, and two-compartment disposition with first-order elimination.
Significant covariates: Asian race on CL/F (+59% vs Whites); log-AST on
CL/F, Vc/F, Vp/F, and F1 (power normalised at LAST = 3.15, i.e., AST ~=
23.3 IU/L); female sex on Vc/F (-44.6% vs males); albumin on Vc/F and
F1; and Asian / Black race on F1 (Asians > Whites > Blacks). Type
of organ transplanted and adult-vs-paediatric population had no
significant effect on PK parameters.
|
|
Tacrolimus
metaanalysis (Nanga 2019)
|
MBMA. Two-compartment population PK meta-model for oral tacrolimus in
solid organ transplantation (Nanga 2019), built from pooled
individual-patient data across 7 historical NONMEM datasets (n = 281
paediatric + adult liver and kidney transplant recipients). Structural
model: first-order absorption with fixed lag time, time-varying
first-order elimination, allometric (WT/50 kg) scaling on apparent
clearance and apparent central volume, multiplicative reduction of CL/F
in hepatic-graft recipients, sigmoidal post-transplant-day recovery of
CL/F, and reduced relative bioavailability for the oral syrup
formulation. The literature-review summary table (Nanga 2019 Table 2: 76
published popPK models) is not used for parameter fitting and is not
reproduced here.
|
|
Tacrolimus
unbound plasma (Sikma 2020)
|
Two-compartment population PK model for whole-blood (Cc), unbound plasma
(Cupc), and total plasma (Ctpc) tacrolimus in 30 adult thoracic-organ
(10 heart + 20 lung) transplant recipients during the first 6
postoperative days (Sikma 2020). First-order oral absorption with ka, F,
and the within-PK fixed-parameter variabilities inherited from a
previously estimated tacrolimus model; non-linear saturable binding of
tacrolimus to erythrocytes (UPC = WBC * Kd / (Bmax * HCT - WBC)) with
the maximum erythrocyte binding capacity Bmax scaled by hematocrit, and
a linear non-specific plasma binding constant Nplasma linking unbound to
total plasma (TPC = Nplasma * UPC).
|
|
Tefibazumab
(Cao 2013)
|
Second-generation minimal physiologically-based PK (mPBPK) model for
tefibazumab in adults (Cao 2013 Model A; clearance from plasma)
|
|
Temozolomide
(Mazzocco 2015)
|
Tumour growth inhibition (TGI) model for low-grade glioma (LGG) treated
with first-line temozolomide chemotherapy (Mazzocco 2015): three
tumour-tissue compartments (proliferative, non-damaged quiescent,
damaged quiescent) coupled to a K-PD virtual drug compartment, with
logistic proliferative growth (carrying capacity K fixed at 100 mm),
treatment-induced damage of both proliferative and quiescent tissues,
time-dependent acquired resistance of the proliferative tissue only, and
tumour-genotype covariate effects of TP53 mutation status on TMZ
efficacy and 1p/19q codeletion status on the
damaged-quiescent-to-proliferative repair rate. Observation is mean
tumour diameter (MTD = P + Q + Qp) in millimetres.
|
|
Theophylline
(Rovei 1982)
|
One-compartment oral PK model for theophylline tablets (Rovei 1982):
first-order absorption with lag time in healthy adult volunteers across
single oral doses of 125-500 mg.
|
|
Ticagrelor
(Almquist 2016)
|
Preclinical (mouse, C57Bl/6 male). Mechanistic interaction PK model for
ticagrelor, its active metabolite (TAM, AR-C124910XX), and the
ticagrelor-neutralising Fab antibody fragment MEDI2452 in mouse
(Almquist 2016). Three-compartment disposition for ticagrelor and TAM
(shared plasma V, tissue V1, V2; V1 in instantaneous equilibrium with
V); MEDI2452 lives in plasma V only and reversibly binds the free
fractions of ticagrelor and TAM with rate kon and dissociation constant
Kd; both free MEDI2452 and the two MEDI2452-drug complexes are
eliminated together at the Fab clearance Cl_f (no recycling).
Naive-pooled fit (no IIV); multiplicative log-normal residual error on
five plasma assays.
|
|
Tisagenlecleucel
(Stein 2019)
|
Cellular kinetic model for tisagenlecleucel CAR-T cells in pediatric and
young adult patients with relapsed or refractory B-cell acute
lymphoblastic leukemia (Stein 2019). Single-infusion
expansion-then-biexponential-decline analytical model: transgene levels
grow exponentially at rate rho up to Tmax, after which effector cells
decline at rate alpha and a fraction FB transitions to memory cells
declining at rate beta.
|
|
Tislelizumab
(Budha 2023)
|
Three-compartment population PK model for intravenous tislelizumab
(anti-PD-1 IgG4) in patients with advanced tumors (Budha 2023)
|
|
Tobra
(Hennig 2013)
|
Two-compartment intravenous population PK model for tobramycin in adults
and children with and without cystic fibrosis (Hennig 2013); fat-free
mass allometric scaling on CL/Q (estimated exponent) and on V1/V2
(linear), sex-specific reference CL and V1, piecewise-linear age effect
on CL with breakpoint at 18 years, and a power effect of the
SCR_mean/SCR ratio on CL.
|
|
Tobramycin
(Hennig 2008)
|
Two-compartment population PK model for once-daily IV tobramycin in
paediatric cystic fibrosis patients (Hennig 2008), with allometric
weight scaling on CL, Q, Vc, and Vper (reference 70 kg, exponent 3/4 for
clearances and 1 for volumes), full-block correlated between-subject
variability on CL/Vc/Vper, a fixed 30 min infusion duration into the
central compartment, and an estimated lag time between infusion start
and drug entry into the patient’s vein.
|
|
Tobramycin
inhaled (Ting 2014)
|
Two-compartment population PK model for inhaled tobramycin powder (TIP /
TOBI Podhaler) in cystic fibrosis patients (Ting 2014), with first-order
absorption from a depot compartment and apparent (post-bioavailability)
clearance and volumes. Body mass index (BMI) and baseline FEV1
percent-predicted are power-form covariates on apparent central volume
of distribution (reference 18.8 kg/m^2 and 62.1 % respectively).
|
|
Tocilizumab
(Frey 2010)
|
Two-compartment population PK model for tocilizumab in adults with
moderate-to-severe rheumatoid arthritis (Frey 2010), with parallel
first-order linear and Michaelis-Menten elimination from the central
compartment.
|
|
Tocilizumab
(Frey 2013)
|
Indirect-response PK/PD model of tocilizumab on the 28-joint Disease
Activity Score (DAS28) in adults with rheumatoid arthritis
(Levi/Grange/Frey 2013, OPTION + TOWARD phase III pool, n = 1703
patients with 12,618 DAS28 observations). Tocilizumab inhibits the DAS28
production rate Kin via a sigmoid Emax function whose driving
concentration is the sum of circulating tocilizumab and a constant DMARD
background term expressed in tocilizumab concentration units. The PK
driver is the two-compartment, parallel linear + Michaelis-Menten model
of Frey 2010 (PMID 20097931), reused unchanged for the exposure-response
analysis.
|
|
Topotecan
(Roberts 2016)
|
One-compartment population pharmacokinetic model for oral topotecan
lactone in infants and very young children with primary central nervous
system tumours (Roberts 2016). First-order absorption into a depot
compartment is followed by first-order elimination from a central
compartment. Apparent volume of distribution (V/F) and apparent
clearance (CL/F) are scaled by body surface area as power functions
centred on the cohort median (0.57 m^2); the ABCG2 rs4148157 G>A
variant (heterozygous AG or homozygous AA carriers pooled vs the GG
reference) carries an exponential covariate effect on the absorption
rate constant Ka, yielding an approximately 2-fold higher Ka in carriers
than in GG homozygotes.
|
|
Torsemide
(Jeong 2022)
|
Two-compartment population PK model for oral torsemide in healthy Korean
adult males (Jeong 2022), with first-order absorption after a lag time,
proportional residual error, and categorical genotype covariates:
OATP1B1 *15 haplotype (intermediate / poor transporter) reduces apparent
central volume, and CYP2C9 extensive-metabolizer phenotype increases
apparent oral clearance and apparent inter-compartmental clearance.
|
|
Tralokinumab
(Soehoel 2022)
|
Two-compartment population PK model for tralokinumab (Soehoel 2022) in
adults with moderate-to-severe atopic dermatitis, with SC first-order
absorption and allometric body-weight effects.
|
|
TranexamicAcid
(Dunn 2025)
|
Two-compartment population PK model for tranexamic acid (TXA) with
parallel first-order intramuscular and first-order oral absorption (oral
lag time) and first-order elimination, in pregnant individuals receiving
IV, IM, or oral TXA for prevention or treatment of postpartum hemorrhage
(Dunn 2025).
|
|
Trastuzumab
(Bruno 2005)
|
Two-compartment linear population PK model for intravenous trastuzumab
in adults with HER2-positive metastatic breast cancer (MBC) or advanced
solid tumors; covariate effects of number of metastatic sites (>= 4)
and baseline HER2 shed extracellular domain (ECD) on clearance, and body
weight and ECD on central volume (Bruno 2005, first published
trastuzumab popPK).
|
|
Trastuzumab
(LeTilly 2021)
|
Two-compartment serum/CSF population PK model for trastuzumab after
intrathecal and intravenous administration in adults with HER2+ breast
cancer leptomeningeal metastases (Le Tilly 2021); zero-order
serum-to-CSF transfer plus first-order CSF-to-serum return, with a
Friberg-style chain of latent target (HER2) transit compartments and
irreversible binding-driven elimination of trastuzumab in the CSF
compartment.
|
|
Trastuzumab
(Quartino 2016)
|
Two-compartment population PK model with parallel linear and
Michaelis-Menten nonlinear elimination from the central compartment and
first-order subcutaneous absorption (with bioavailability) for
trastuzumab (Herceptin) administered IV or as a fixed 600 mg
manual-syringe SC dose in women with HER2-positive early breast cancer;
covariates body weight (on CL, Vc, Vp) and ALT (on CL) (Quartino 2016,
HannaH study)
|
|
Trastuzumab
(Quartino 2019)
|
Two-compartment population PK model with parallel linear and
Michaelis-Menten nonlinear elimination from the central compartment for
intravenous trastuzumab (Herceptin) in patients with metastatic breast
cancer, early breast cancer, advanced gastric cancer, or other solid
tumors (Quartino 2019)
|
|
Trastuzumab
(Reijers 2016)
|
Three-compartment population PK model with parallel linear and
Michaelis-Menten nonlinear elimination from the central compartment for
intravenous trastuzumab in healthy male volunteers from a phase I
biosimilarity trial of the FTMB biosimilar vs Herceptin reference
product (Reijers 2016, combined model on all dose levels 0.49-6.44
mg/kg); covariates are lean body mass on central volume of distribution
V1 and BMI on the linear elimination rate constant ke.
|
|
Trastuzumab
skbr3 (FehlingKaschek 2019)
|
In vitro (SKBR3 cell line). Mechanistic ODE model of trastuzumab-induced
HER2 receptor internalization with two cell-membrane phenotypes (ruffled
vs flat); Model B of Fehling-Kaschek 2019, no recycling or degradation.
|
|
TrastuzumabDeruxtecan
(Yin 2021)
|
Two-compartment population PK model for intact trastuzumab deruxtecan
(T-DXd, DS-8201, anti-HER2 antibody-drug conjugate) with linear
elimination and covariate effects of body weight, albumin, baseline
tumor size, sex, and Japan-country indicator in patients with
HER2-positive breast cancer or other HER2-expressing solid tumors (Yin
2021)
|
|
Trastuzumabemtansine
(Lu 2014)
|
Linear two-compartment population PK model of trastuzumab emtansine
(T-DM1, anti-HER2 antibody-drug conjugate) with first-order elimination
from the central compartment in patients with HER2-positive locally
advanced or metastatic breast cancer (Lu 2014)
|
|
TrastuzumabEmtansine
mechanistic (Bender 2014)
|
Mechanistic DAR0-DAR7 catenary deconjugation PK model for trastuzumab
emtansine (T-DM1) in cynomolgus monkeys (default) and rats (Bender
2014): each DAR moiety distributes into a shared three-compartment
backbone and deconjugates sequentially toward naked trastuzumab (DAR0);
uses five shared upper-chain rate constants (k7->3) plus separate
k_2->1 and k_1->0.
|
|
TrastuzumabEmtansine
reduced (Bender 2014)
|
Reduced three-compartment population PK model for trastuzumab emtansine
(T-DM1) and naked trastuzumab (DAR0) in cynomolgus monkeys (default) and
rats (Bender 2014): single lumped T-DM1 conjugate species deconjugates
into DAR0 via a single deconjugation clearance; both species share
V1/V2/V3 and distributional clearances.
|
|
Tremelimumab
(Hwang 2022)
|
Two-compartment population PK model for tremelimumab (anti-CTLA-4 IgG2
kappa) with regimen-dependent sigmoidal time-varying clearance in adults
with advanced solid tumours, dosed as monotherapy or in combination with
durvalumab (Hwang 2022)
|
|
Trontinemab
(Grimm 2023)
|
Trontinemab PK model in non-human primates (Grimm 2023): two-compartment
plasma PK with Michaelis-Menten elimination and brain-region
effect-compartment distribution (cerebellum, hippocampus, striatum,
cortex, choroid plexus, CSF).
|
|
Tusamitamab
(Pouzin 2022)
|
Integrated multi-analyte semi-mechanistic population PK model of
tusamitamab ravtansine (SAR408701, anti-CEACAM5 IgG1-SPDB-DM4 ADC) in
adults with advanced solid tumors (Pouzin 2022): explicit
two-compartment disposition for DAR1-DAR8 ADC species and a separate
naked-antibody (NAB) chain sharing Vc/Vp/Q, irreversible first-order
DAR_n -> DAR_(n-1) deconjugation feeding a one-compartment DM4
catabolite that converts to MeDM4.
|
|
UDCA
(Zuo 2016)
|
Systems model. Enterohepatic recirculation of ursodeoxycholic acid
(UDCA) and its glycine (GUDCA) and taurine (TUDCA) conjugates in healthy
adults, with adaptation to primary biliary cirrhosis (PBC). 19 ODEs
across stomach, intestine, portal vein, blood, liver, biliary system,
and feces compartments per analyte; oral square-wave absorption (0.5 h)
and meal/snack-modulated biliary-to-intestinal flux. No IIV or residual
error - typical-value mechanistic simulation only.
|
|
Ustekinumab
(Aguiar 2021)
|
Population pharmacokinetic-pharmacodynamic model for ustekinumab in
adults with Crohn’s disease (Aguiar 2021): two-compartment
quasi-equilibrium TMDD model for ustekinumab and the unbound IL-12/IL-23
p40 target, linked to fecal calprotectin via an indirect-response model
with target-driven stimulation of FC production.
|
|
Valganciclovir
(Vezina 2010)
|
One-compartment population PK model for ganciclovir following oral
valganciclovir prophylaxis in pediatric solid organ transplant
recipients at risk for Epstein-Barr virus disease (Vezina 2010).
First-order absorption with no covariates retained in the final model;
doses are mg of valganciclovir uncorrected for molecular weight, and the
apparent CL/F and V/F absorb both oral bioavailability and the molar
conversion from valganciclovir to ganciclovir.
|
|
Valganciclovir
(Vezina 2014)
|
Two-compartment population PK model for ganciclovir after oral
valganciclovir prophylaxis in paediatric and adult solid organ
transplant recipients (Vezina 2014). First-order absorption with fixed
lag time and rate, allometric (WT/70 kg) scaling on apparent CL/F and
Q/F (exponent 0.75) and on V2/F and V3/F (exponent 1.0), and a
power-form effect of body-weight-adjusted creatinine clearance on CL/F
(reference 60 mL/min).
|
|
Vancomycin
(Goti 2018)
|
Two-compartment IV population PK model for vancomycin in hospitalized
adults with and without intermittent hemodialysis (Goti 2018). Volumes
scaled allometrically to body weight (reference 70 kg, fixed linear
exponent), CL scaled by Cockcroft-Gault creatinine clearance with a
power exponent (reference 120 mL/min), and intermittent hemodialysis
acts as a multiplicative factor on CL (0.7) and central volume (0.5).
|
|
Vancomycin
(Moore 2016)
|
Two-compartment IV population PK model for vancomycin in adult patients
on extracorporeal membrane oxygenation (ECMO) therapy (Moore 2016).
Linear (additive) covariate effects on CL (Cockcroft-Gault creatinine
clearance), Vc, and Vp (body weight), each centered on the cohort median
(CRCL 84 mL/min; WT 95 kg). Proportional residual error; IIV on CL and
Vc only (Q and Vp had no IIV).
|
|
Vedolizumab
(Rosario 2015)
|
Two-compartment population PK model for vedolizumab (humanised
anti-alpha4-beta7 integrin IgG1 monoclonal antibody) with parallel
linear and Michaelis-Menten elimination in adults with
moderately-to-severely active ulcerative colitis or Crohn’s disease and
healthy volunteers (Rosario 2015).
|
|
Visilizumab
(Cao 2013)
|
Second-generation minimal physiologically-based PK (mPBPK) model for
visilizumab in adults (Cao 2013 Model A; clearance from plasma)
|
|
Vismodegib
(Lu 2015)
|
Semi-mechanism-based one-compartment population pharmacokinetic model
for vismodegib (GDC-0449, oral Hedgehog pathway inhibitor) in adults
with advanced solid tumors and healthy volunteers. First-order
absorption, first-order elimination of unbound drug, and saturable
fast-equilibrium binding to alpha-1-acid glycoprotein (AAG) jointly
describe total and unbound plasma vismodegib concentrations. AAG is
supplied as a time-varying covariate (uM); covariates retained on
disposition are age (power on CLunbound, reference 60 years) and body
weight (power on Vc, reference 75 kg); formulation (Phase I dry-blend
capsule vs Phase II wet-granulation commercial capsule) and population
(healthy volunteer vs patient) shift Ka and relative bioavailability F
(Lu 2015).
|
|
Voriconazole
(Akbar 2025)
|
One-compartment population pharmacokinetic model with first-order
elimination for intravenous voriconazole in adult and pediatric
Pakistani cancer patients receiving therapeutic drug monitoring (Akbar
2025); creatinine clearance and primary cancer diagnosis are covariates
on clearance
|
|
Voriconazole
(Chen 2015)
|
One-compartment population pharmacokinetic model with first-order
elimination for intravenous voriconazole in Chinese adult critically ill
patients with pulmonary disease (Chen 2015); direct bilirubin enters as
a power-form covariate on clearance.
|
|
Vortioxetine
(Naik 2016)
|
Two-compartment population PK model for vortioxetine in adult patients
with major depressive disorder or generalized anxiety disorder, with
first-order oral absorption, region-specific oral clearance, and linear
creatinine-clearance and height effects on CL/F (Naik 2016)
|
|
Vrc01
(Huang 2017)
|
Two-compartment population PK model for VRC01 (HIV-1 broadly
neutralizing IgG1 monoclonal antibody) in healthy adults after IV or SC
administration (Huang 2017)
|
|
VRC07523LS
(Huynh 2026)
|
Two-compartment population PK model with zero-order subcutaneous
absorption, allometric weight scaling, and binary effects of age (adult
vs infant) and repeat dosing for the broadly neutralizing HIV-1
monoclonal antibody VRC07-523LS in healthy adults and HIV-exposed
infants (Huynh 2026).
|
|
Warfarin
(Xia 2024)
|
K-PD warfarin PK/PD model for adult Han Chinese
(Alfalfa-Warfarin-PPK/PD; Xia 2024). PK parameters fixed from the
Hamberg model; PD EC50 re-estimated, with VKORC1 -1639 G/A and CYP2C9
1/2/*3 allele-specific contributions, body-weight power
scaling, and amiodarone effect on EC50. Two parallel coagulation-factor
transit chains drive INR.
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Zenocutuzumab
(deVriesSchultink 2020)
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Two-compartment population PK model with parallel linear and
Michaelis-Menten non-linear elimination from the central compartment for
intravenous zenocutuzumab (MCLA-128), a bispecific IgG1 (anti-HER2 x
anti-HER3) monoclonal antibody, in patients with various advanced solid
tumors (de Vries Schultink 2020)
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Zolbetuximab
(Yamada 2025)
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Two-compartment population PK model of zolbetuximab (anti-CLDN18.2 IgG1
mAb) with zero-order IV input and time-dependent clearance in patients
with locally advanced unresectable or metastatic
gastric/gastroesophageal junction (G/GEJ) adenocarcinoma (Yamada 2025)
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