caffsim R package: Simulation of Plasma Caffeine Concentrations by Using Population Pharmacokinetic Model

Simulate plasma caffeine concentrations using population pharmacokinetic model described in Lee, Kim, Perera, McLachlan and Bae (2015) doi:10.1007/s00431-015-2581-x and the package was published doi:10.12793/tcp.2017.25.3.141.

• Github: https://github.com/asancpt/caffsim
• Package vignettes and references by pkgdown: http://asancpt.github.io/caffsim

Installation

install.pacakges("devtools")
devtools::install_github("asancpt/caffsim")

# Simply create single dose dataset
caffsim::caffPkparam(Weight = 20, Dose = 200, N = 20) 

# Simply create multiple dose dataset
caffsim::caffPkparamMulti(Weight = 20, Dose = 200, N = 20, Tau = 12) 

Single dose

Create a PK dataset for caffeine single dose

library(caffsim)
MyDataset <- caffPkparam(Weight = 20, Dose = 200, N = 20)
head(MyDataset)

## # A tibble: 6 x 9
##   subjid  Tmax  Cmax   AUC Half_life    CL     V    Ka     Ke
##    <int> <dbl> <dbl> <dbl>     <dbl> <dbl> <dbl> <dbl>  <dbl>
## 1      1 0.183  16.1 191.       8.07  1.05  12.2 32.5  0.0858
## 2      2 0.532  11.2  82.8      4.75  2.41  16.6  7.58 0.146 
## 3      3 2.36   10.2 150.       8.33  1.34  16.1  1.22 0.0832
## 4      4 0.731  10.5  62.8      3.60  3.19  16.6  4.51 0.192 
## 5      5 0.599  12.9  62.0      2.89  3.23  13.4  5.46 0.240 
## 6      6 1.08   12.4 104.       5.01  1.92  13.9  2.99 0.138

Create a dataset for concentration-time curve

MyConcTime <- caffConcTime(Weight = 20, Dose = 200, N = 20)
head(MyConcTime)

## # A tibble: 6 x 3
##   Subject  Time  Conc
##     <dbl> <dbl> <dbl>
## 1       1   0    0   
## 2       1   0.1  6.46
## 3       1   0.2 10.2 
## 4       1   0.3 12.4 
## 5       1   0.4 13.5 
## 6       1   0.5 14.1

Create a concentration-time curve

caffPlot(MyConcTime)

Create plots for publication (according to the amount of caffeine)

• cowplot package is required

#install.packages("cowplot") # if you don't have it
library(cowplot)

MyPlotPub <- lapply(
  c(seq(100, 800, by = 100)), 
  function(x) caffPlotMulti(caffConcTime(20, x, 20)) + 
    theme(legend.position="none") + 
    labs(title = paste0("Single Dose ", x, "mg")))

plot_grid(MyPlotPub[[1]], MyPlotPub[[2]],
          MyPlotPub[[3]], MyPlotPub[[4]],
          MyPlotPub[[5]], MyPlotPub[[6]],
          MyPlotPub[[7]], MyPlotPub[[8]],
          labels=LETTERS[1:8], ncol = 2, nrow = 4)

Multiple dose

Create a PK dataset for caffeine multiple doses

MyDatasetMulti <- caffPkparamMulti(Weight = 20, Dose = 200, N = 20, Tau = 12)
head(MyDatasetMulti)

## # A tibble: 6 x 9
##   subjid TmaxS CmaxS  AUCS    AI Aavss Cavss Cmaxss Cminss
##    <int> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl>  <dbl>  <dbl>
## 1      1 1.20   10.2  75.9  1.16 102.   6.32   14.4   2.04
## 2      2 2.56   12.0 165.   1.50 181.  13.7    22.7   7.51
## 3      3 0.193  15.0 105.   1.21 114.   8.75   18.6   3.21
## 4      4 1.04   12.9  86.0  1.13  92.1  7.17   17.5   2.01
## 5      5 1.10   13.9 114.   1.22 116.   9.51   19.9   3.58
## 6      6 0.804  12.9 103.   1.23 119.   8.62   17.8   3.33

Create a dataset for concentration-time curve

MyConcTimeMulti <- caffConcTimeMulti(Weight = 20, Dose = 200, N = 20, Tau = 12, Repeat = 10)
head(MyConcTimeMulti)

## # A tibble: 6 x 3
## # Groups:   Subject [1]
##   Subject  Time  Conc
##     <dbl> <dbl> <dbl>
## 1       1   0    0   
## 2       1   0.1  6.76
## 3       1   0.2 10.8 
## 4       1   0.3 13.1 
## 5       1   0.4 14.5 
## 6       1   0.5 15.2

Create a concentration-time curve

caffPlotMulti(MyConcTimeMulti)

Create plots for publication (according to dosing interval)

• cowplot package is required

#install.packages("cowplot") # if you don't have it
library(cowplot)

MyPlotMultiPub <- lapply(
  c(seq(4, 32, by = 4)), 
  function(x) caffPlotMulti(caffConcTimeMulti(20, 250, 20, x, 15)) + 
    theme(legend.position="none") + 
    labs(title = paste0("q", x, "hr" )))

plot_grid(MyPlotMultiPub[[1]], MyPlotMultiPub[[2]],
          MyPlotMultiPub[[3]], MyPlotMultiPub[[4]],
          MyPlotMultiPub[[5]], MyPlotMultiPub[[6]],
          MyPlotMultiPub[[7]], MyPlotMultiPub[[8]],
          labels=LETTERS[1:8], ncol = 2, nrow = 4)

Interactive shiny app

caffShiny()