Add linear indirect response model
Arguments
- ui
rxode2 model
- stim
what type of stimulation indirect response model:
- `in`: stimulation of input
- `out`: stimulation of output
- inhib
what type of inhibition indirect response model:
- `in`: inhibition of input
- `out`: inhibition of output
- ek
simulation linear constant
- ik
inhibition linear constant
- kin
this is the kin parameter name
- kout
this is the kout parameter name
- cc
the concentration value
- R
drug response compartment
- effect
the effect variable that will be modeled
Value
model with linear indirect effect added
Note that while linear indirect effects are not common, it allows an easier hook to produce other standard effect curves like Emax/Imax, Hill, etc.
See also
Other Indirect response:
addIndirect(),
convertKinR0()
Examples
readModelDb("PK_2cmt_no_depot") |> addIndirectLin(stim="in")
#>
#>
#> ── rxode2-based free-form 3-cmt ODE model ──────────────────────────────────────
#> ── Initalization: ──
#> Fixed Effects ($theta):
#> lcl lvc lvp lq propSd lkin lkout lEk
#> 1.0 3.0 5.0 0.1 0.5 0.1 0.1 0.1
#> effectSd
#> 0.1
#>
#> States ($state or $stateDf):
#> Compartment Number Compartment Name
#> 1 1 central
#> 2 2 peripheral1
#> 3 3 R
#> ── Multiple Endpoint Model ($multipleEndpoint): ──
#> variable cmt dvid*
#> 1 Cc ~ … cmt='Cc' or cmt=4 dvid='Cc' or dvid=1
#> 2 effect ~ … cmt='effect' or cmt=5 dvid='effect' or dvid=2
#> * If dvids are outside this range, all dvids are re-numered sequentially, ie 1,7, 10 becomes 1,2,3 etc
#>
#> ── Model (Normalized Syntax): ──
#> function() {
#> ini({
#> lcl <- 1
#> label("Clearance (CL)")
#> lvc <- 3
#> label("Central volume of distribution (V)")
#> lvp <- 5
#> label("Peripheral volume of distribution (Vp)")
#> lq <- 0.1
#> label("Intercompartmental clearance (Q)")
#> propSd <- c(0, 0.5)
#> label("Proportional residual error (fraction)")
#> lkin <- 0.1
#> label("zero order response production(kin)")
#> lkout <- 0.1
#> label("first order rate response loss (kout)")
#> lEk <- 0.1
#> label("linear effect constant (Ek)")
#> effectSd <- c(0, 0.1)
#> label("additive error for effect")
#> })
#> model({
#> kin <- exp(lkin)
#> kout <- exp(lkout)
#> Ek <- exp(lEk)
#> cl <- exp(lcl)
#> vc <- exp(lvc)
#> vp <- exp(lvp)
#> q <- exp(lq)
#> kel <- cl/vc
#> k12 <- q/vc
#> k21 <- q/vp
#> d/dt(central) <- -kel * central - k12 * central + k21 *
#> peripheral1
#> d/dt(peripheral1) <- k12 * central - k21 * peripheral1
#> Cc <- central/vc
#> Cc ~ prop(propSd)
#> R(0) <- kin/kout
#> d/dt(R) <- kin * (1 + Ek * Cc) - kout * R
#> effect <- R
#> effect ~ add(effectSd)
#> })
#> }
readModelDb("PK_2cmt_no_depot") |> addIndirectLin(stim="out")
#>
#>
#> ── rxode2-based free-form 3-cmt ODE model ──────────────────────────────────────
#> ── Initalization: ──
#> Fixed Effects ($theta):
#> lcl lvc lvp lq propSd lkin lkout lEk
#> 1.0 3.0 5.0 0.1 0.5 0.1 0.1 0.1
#> effectSd
#> 0.1
#>
#> States ($state or $stateDf):
#> Compartment Number Compartment Name
#> 1 1 central
#> 2 2 peripheral1
#> 3 3 R
#> ── Multiple Endpoint Model ($multipleEndpoint): ──
#> variable cmt dvid*
#> 1 Cc ~ … cmt='Cc' or cmt=4 dvid='Cc' or dvid=1
#> 2 effect ~ … cmt='effect' or cmt=5 dvid='effect' or dvid=2
#> * If dvids are outside this range, all dvids are re-numered sequentially, ie 1,7, 10 becomes 1,2,3 etc
#>
#> ── Model (Normalized Syntax): ──
#> function() {
#> ini({
#> lcl <- 1
#> label("Clearance (CL)")
#> lvc <- 3
#> label("Central volume of distribution (V)")
#> lvp <- 5
#> label("Peripheral volume of distribution (Vp)")
#> lq <- 0.1
#> label("Intercompartmental clearance (Q)")
#> propSd <- c(0, 0.5)
#> label("Proportional residual error (fraction)")
#> lkin <- 0.1
#> label("zero order response production(kin)")
#> lkout <- 0.1
#> label("first order rate response loss (kout)")
#> lEk <- 0.1
#> label("linear effect constant (Ek)")
#> effectSd <- c(0, 0.1)
#> label("additive error for effect")
#> })
#> model({
#> kin <- exp(lkin)
#> kout <- exp(lkout)
#> Ek <- exp(lEk)
#> cl <- exp(lcl)
#> vc <- exp(lvc)
#> vp <- exp(lvp)
#> q <- exp(lq)
#> kel <- cl/vc
#> k12 <- q/vc
#> k21 <- q/vp
#> d/dt(central) <- -kel * central - k12 * central + k21 *
#> peripheral1
#> d/dt(peripheral1) <- k12 * central - k21 * peripheral1
#> Cc <- central/vc
#> Cc ~ prop(propSd)
#> R(0) <- kin/kout
#> d/dt(R) <- kin - kout * R * (1 + Ek * Cc)
#> effect <- R
#> effect ~ add(effectSd)
#> })
#> }
readModelDb("PK_2cmt_no_depot") |> addIndirectLin(inhib="in")
#>
#>
#> ── rxode2-based free-form 3-cmt ODE model ──────────────────────────────────────
#> ── Initalization: ──
#> Fixed Effects ($theta):
#> lcl lvc lvp lq propSd lkin lkout lIk
#> 1.0 3.0 5.0 0.1 0.5 0.1 0.1 0.1
#> effectSd
#> 0.1
#>
#> States ($state or $stateDf):
#> Compartment Number Compartment Name
#> 1 1 central
#> 2 2 peripheral1
#> 3 3 R
#> ── Multiple Endpoint Model ($multipleEndpoint): ──
#> variable cmt dvid*
#> 1 Cc ~ … cmt='Cc' or cmt=4 dvid='Cc' or dvid=1
#> 2 effect ~ … cmt='effect' or cmt=5 dvid='effect' or dvid=2
#> * If dvids are outside this range, all dvids are re-numered sequentially, ie 1,7, 10 becomes 1,2,3 etc
#>
#> ── Model (Normalized Syntax): ──
#> function() {
#> ini({
#> lcl <- 1
#> label("Clearance (CL)")
#> lvc <- 3
#> label("Central volume of distribution (V)")
#> lvp <- 5
#> label("Peripheral volume of distribution (Vp)")
#> lq <- 0.1
#> label("Intercompartmental clearance (Q)")
#> propSd <- c(0, 0.5)
#> label("Proportional residual error (fraction)")
#> lkin <- 0.1
#> label("zero order response production(kin)")
#> lkout <- 0.1
#> label("first order rate response loss (kout)")
#> lIk <- c(-Inf, 0.1, 1)
#> label("linear inhibition constant (Ik)")
#> effectSd <- c(0, 0.1)
#> label("additive error for effect")
#> })
#> model({
#> kin <- exp(lkin)
#> kout <- exp(lkout)
#> Ik <- exp(lIk)
#> cl <- exp(lcl)
#> vc <- exp(lvc)
#> vp <- exp(lvp)
#> q <- exp(lq)
#> kel <- cl/vc
#> k12 <- q/vc
#> k21 <- q/vp
#> d/dt(central) <- -kel * central - k12 * central + k21 *
#> peripheral1
#> d/dt(peripheral1) <- k12 * central - k21 * peripheral1
#> Cc <- central/vc
#> Cc ~ prop(propSd)
#> R(0) <- kin/kout
#> d/dt(R) <- kin * (1 - Ik * Cc) - kout * R
#> effect <- R
#> effect ~ add(effectSd)
#> })
#> }
readModelDb("PK_2cmt_no_depot") |> addIndirectLin(inhib="out")
#>
#>
#> ── rxode2-based free-form 3-cmt ODE model ──────────────────────────────────────
#> ── Initalization: ──
#> Fixed Effects ($theta):
#> lcl lvc lvp lq propSd lkin lkout lIk
#> 1.0 3.0 5.0 0.1 0.5 0.1 0.1 0.1
#> effectSd
#> 0.1
#>
#> States ($state or $stateDf):
#> Compartment Number Compartment Name
#> 1 1 central
#> 2 2 peripheral1
#> 3 3 R
#> ── Multiple Endpoint Model ($multipleEndpoint): ──
#> variable cmt dvid*
#> 1 Cc ~ … cmt='Cc' or cmt=4 dvid='Cc' or dvid=1
#> 2 effect ~ … cmt='effect' or cmt=5 dvid='effect' or dvid=2
#> * If dvids are outside this range, all dvids are re-numered sequentially, ie 1,7, 10 becomes 1,2,3 etc
#>
#> ── Model (Normalized Syntax): ──
#> function() {
#> ini({
#> lcl <- 1
#> label("Clearance (CL)")
#> lvc <- 3
#> label("Central volume of distribution (V)")
#> lvp <- 5
#> label("Peripheral volume of distribution (Vp)")
#> lq <- 0.1
#> label("Intercompartmental clearance (Q)")
#> propSd <- c(0, 0.5)
#> label("Proportional residual error (fraction)")
#> lkin <- 0.1
#> label("zero order response production(kin)")
#> lkout <- 0.1
#> label("first order rate response loss (kout)")
#> lIk <- c(-Inf, 0.1, 1)
#> label("linear inhibition constant (Ik)")
#> effectSd <- c(0, 0.1)
#> label("additive error for effect")
#> })
#> model({
#> kin <- exp(lkin)
#> kout <- exp(lkout)
#> Ik <- exp(lIk)
#> cl <- exp(lcl)
#> vc <- exp(lvc)
#> vp <- exp(lvp)
#> q <- exp(lq)
#> kel <- cl/vc
#> k12 <- q/vc
#> k21 <- q/vp
#> d/dt(central) <- -kel * central - k12 * central + k21 *
#> peripheral1
#> d/dt(peripheral1) <- k12 * central - k21 * peripheral1
#> Cc <- central/vc
#> Cc ~ prop(propSd)
#> R(0) <- kin/kout
#> d/dt(R) <- kin - kout * R * (1 - Ik * Cc)
#> effect <- R
#> effect ~ add(effectSd)
#> })
#> }