R/pk_2cmt_inf.R

In InsightRX/clinPK: Clinical Pharmacokinetics Toolkit

#' Concentration predictions for 2-compartmental PK model, single or multiple infusions
#'
#' @param t vector of time
#' @param dose dose
#' @param tau dosing interval
#' @param t_inf infusion time
#' @param CL clearance
#' @param V volume of central compartment
#' @param Q inter-compartimental clearance
#' @param V2 volume of peripheral compartment
#' @param ruv residual error (list)
#' @export
pk_2cmt_inf <- function(
    t = c(0:24),
    dose = 100,
    tau = 12,
    t_inf = 1,
    CL = 3,
    V = 30,
    Q = 2,
    V2 = 20,
    ruv = NULL
  ) {
  k <- CL / V
  tmp <- c()
  dat <- data.frame(t = t, dv = 0)
  t_dos <- t %% tau
  n_dos <- floor(t/tau)
  unq_dos <- unique(n_dos) + 1

  # reparametrization:
  terms <- (Q/V) + (Q/V2) + (CL/V)
  beta <- 0.5 * (terms - sqrt(terms^2 - 4*(Q/V2)*(CL/V)))
  alpha <- ((Q/V2)*(CL/V))/beta
  A <- (1/V) * (alpha - (Q/V2))/(alpha-beta)
  B <- (1/V) * ((beta - Q/V2)/(beta-alpha))

  for(i in 1:(length(unq_dos)-1)) {
    sel <- n_dos >= i-1
    tmp <- dat[sel,]
    tmp$t <- tmp$t - (i-1)*tau

    ## equation:
    tmp[tmp$t <= t_inf,]$dv <-
      (dose/t_inf) * (
        (A/alpha) * (1-exp(-alpha*tmp$t[tmp$t <= t_inf])) +
        (B/beta)  * (1-exp(-beta *tmp$t[tmp$t <= t_inf]))
      )
    tmp[tmp$t > t_inf,]$dv <-
      (dose/t_inf) * (
        (A/alpha) * (1-exp(-alpha*t_inf)) * exp(-alpha * (tmp$t[tmp$t > t_inf] - t_inf)) +
        (B/beta)  * (1-exp(-beta *t_inf)) * exp(-beta  * (tmp$t[tmp$t > t_inf] - t_inf))
      )
    dat[sel,]$dv <- dat[sel,]$dv + tmp$dv
  }

  if(!is.null(ruv)) {
    dat$dv <- add_ruv (dat$dv, ruv)
  }
  return(dat)
}