R/strip_curves.R

In metrumresearchgroup/PKPDmisc: Pharmacokinetic and Pharmacodynamic Data Management Functions

#' basic curve stripping to get initial estimates
#' @param .time column for time
#' @param .dv column for DV (concentration) values
#' @param dose Dose value or column
#' @param number_terminal_points number of points in terminal phase
#' @param oral whether data is oral (instead of IV)
#' @param round number of decimals to round, default to 2
#' @export
#' @details
#' for oral stripping, if multiple cmax values found per ID, will use the first
#' @examples 
#' \dontrun{
#' strip_curves(df$TIME, df$DV, dose =1000, 5, oral=TRUE)
#' df %>% group_by(ID) %>% do(data.frame(strip_curves(.$TIME, .$DV, 1000, 5, TRUE)))
#' }
strip_curves <- function(.time, .dv, dose, number_terminal_points, oral= FALSE, round = 2) {
  
  num_time_points <- length(.time)
  #check to make sure partial .time legit option
  ###need to add warning
  start_terminal_points <- num_time_points - number_terminal_points + 1
  
  
  terminal_time<-.time[start_terminal_points:num_time_points]
  terminal_dv <- .dv[start_terminal_points:num_time_points]
  terminal_xt <-lm(log(terminal_dv)~terminal_time) # log-linear terminal phase calculation for k
  terminal_lambda_z<- as.numeric(terminal_xt$coef[2])
  
  predicted_terminal_portion <- exp(predict(terminal_xt, data.frame(terminal_time = .time)))
  remaining_alpha_dv <- .dv- predicted_terminal_portion
  
  alpha_index <- 1:(num_time_points - number_terminal_points)
  if(oral) {
    # cmax to last point not in terminal phase 
    alpha_index <- which(.dv==max(.dv))[1]:(num_time_points - number_terminal_points)
  }
  alpha_dv <- remaining_alpha_dv[alpha_index]
  alpha_t <- .time[alpha_index]
  alpha_xt <- lm(log(alpha_dv)~alpha_t)
  
  A <- exp(unlist(alpha_xt$coef[1]))
  B <- exp(unlist(terminal_xt$coef[1]))
  alpha <- -as.numeric(unlist(alpha_xt$coef[2]))
  beta <- -as.numeric(unlist(terminal_xt$coef[2]))
  
  k21 <- (A*beta + B*alpha)/(A+B)
  kel <- alpha*beta/k21
  k12 <- alpha + beta - k21 - kel
  
  Vc <- dose/max(.dv)
  Vp <-  k12/k21*Vc
  Q <- k12*Vc
  CL <- kel*Vc
  
  initial_estimates <- data.frame("Vc" = mean(Vc), "Vp" = mean(Vp), "Q" = mean(Q), "CL" = mean(CL))
  row.names(initial_estimates) <- NULL
  return(round(initial_estimates, round))
}