Add a second absorption path for double-absorption models

Adds a parallel absorption path (`depot2`) to a model that already has first-order absorption through `depot`, for Monolix-style double-absorption models: one dose record is split at translation time into two parallel inputs with a logit-parameterized `F1` apportionment. The second path can itself be zero-order (`type = "zero"`, a modeled `dur(depot2)` input), first-order (`type = "first"`, `ka2`), or a transit chain (`delay = "transit"`), with an optional lag.

Usage

addSecondAbsorption(
  ui,
  type = c("first", "zero"),
  delay = c("none", "lag", "transit"),
  n = NULL,
  central = "central",
  depot = "depot",
  depot2 = "depot2",
  ka = "ka",
  ka2 = "ka2",
  tk0 = "tk0",
  f1 = 0.7
)

Arguments

ui: The model as a function (or something convertible to an rxUi object)
type: second-path input type: `"zero"` for a zero-order (modeled-duration) input or `"first"` for a first-order (`ka2`) input
delay: second-path delay: `"none"`, `"lag"` (an `alag` on the second path), or `"transit"` (a transit chain feeding the second path)
n: number of transit compartments when `delay = "transit"`
central: central compartment name
depot: depot compartment name
depot2: name of the second depot compartment
ka: absorption rate parameter name
ka2: name of the second first-order absorption rate
tk0: name of the zero-order duration on the second path
f1: initial fraction of the dose entering the first path, in (0,1)

Value

a model with two parallel absorption paths

Details

Only one second absorption path is supported per model; applying this twice raises an error.

Author

Matthew L. Fidler

Examples


# simultaneous zero-order + first-order (Monolix double absorption)
readModelDb("PK_1cmt_des") |>
  addSecondAbsorption(type = "first", delay = "lag", f1 = 0.7)
#>  
#>  
#>  ── rxode2-based free-form 3-cmt ODE model ────────────────────────────────────── 
#>  ── Initalization: ──  
#> Fixed Effects ($theta): 
#>         lka         lcl         lvc      propSd        lka2  llagDepot2 
#>   0.4500000   1.0000000   3.4500000   0.5000000   0.1000000   0.1000000 
#> logitfDepot 
#>   0.8472979 
#> 
#> States ($state or $stateDf): 
#>   Compartment Number Compartment Name
#> 1                  1            depot
#> 2                  2           depot2
#> 3                  3          central
#>  ── Model (Normalized Syntax): ── 
#> function() {
#>     compartmentData <- list(depot = list(analyte = "drug", units = NA_character_, 
#>         specimen = "administration site", verified = FALSE), 
#>         central = list(analyte = "drug", units = NA_character_, 
#>             specimen = "plasma", verified = FALSE))
#>     dosing <- c("central", "depot")
#>     reference <- "nlmixr2lib template"
#>     units <- list(time = "time_unit", dosing = "dose_unit", concentration = "conc_unit/vol_unit")
#>     ini({
#>         lka <- 0.45
#>         label("Absorption rate (Ka)")
#>         lcl <- 1
#>         label("Clearance (CL)")
#>         lvc <- 3.45
#>         label("Central volume of distribution (V)")
#>         propSd <- c(0, 0.5)
#>         label("Proportional residual error (fraction)")
#>         lka2 <- 0.1
#>         label("First order absorption rate (ka2)")
#>         llagDepot2 <- 0.1
#>         logitfDepot <- 0.847297860387204
#>         label("Fraction of dose absorbed from depot (fDepot)")
#>     })
#>     model({
#>         fDepot <- expit(logitfDepot, 0, 1)
#>         lagDepot2 <- exp(llagDepot2)
#>         ka <- exp(lka)
#>         cl <- exp(lcl)
#>         vc <- exp(lvc)
#>         kel <- cl/vc
#>         splitInfusionBolus(depot, depot, depot2)
#>         d/dt(depot) <- -ka * depot
#>         f(depot) <- fDepot
#>         ka2 <- exp(lka2)
#>         d/dt(depot2) <- -ka2 * depot2
#>         f(depot2) <- 1 - fDepot
#>         lag(depot2) <- lagDepot2
#>         d/dt(central) <- ka * depot - kel * central + ka2 * depot2
#>         Cc <- central/vc
#>         Cc ~ prop(propSd)
#>     })
#> }