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)

subjid	Tmax	Cmax	AUC	Half_life	CL	V	Ka	Ke
1	0.9858664	15.006075	115.44184	4.594639	1.732474	11.48643	3.2719387	0.1508280
2	3.8148250	7.699503	107.02942	6.354802	1.868645	17.13545	0.5169846	0.1090514
3	0.8826191	12.147005	107.60372	5.491894	1.858672	14.72962	4.0586205	0.1261860
4	0.2567103	13.950749	139.11091	6.730028	1.437702	13.96215	20.7765914	0.1029713
5	1.1563495	8.302007	65.44492	4.587332	3.056005	20.22931	2.6177408	0.1510682
6	1.2026953	9.445008	55.68603	3.130858	3.591565	16.22609	2.0869246	0.2213451

Create a dataset for concentration-time curve

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

Subject	Time	Conc
1	0.0	0.000000
1	0.1	4.129452
1	0.2	7.174502
1	0.3	9.410497
1	0.4	11.042950
1	0.5	12.225252

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)

subjid	TmaxS	CmaxS	AUCS	AI	Aavss	Cavss	Cmaxss	Cminss
1	0.9548818	14.35410	78.14388	1.068908	72.79768	6.511990	19.08368	1.230238
2	1.1467783	11.52173	89.29910	1.187191	108.04592	7.441592	16.31939	2.573172
3	0.6768031	16.69770	136.35979	1.250128	124.04012	11.363316	22.85721	4.573316
4	0.7753311	14.44837	119.92576	1.251847	124.46355	9.993813	20.06162	4.036002
5	0.2400863	13.36207	65.42138	1.081913	77.33312	5.451782	15.22267	1.152520
6	0.6535510	10.73536	76.56109	1.183885	107.17374	6.380091	14.06610	2.184791

Create a dataset for concentration-time curve

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

Subject	Time	Conc
1	0.0	0.000000
1	0.1	4.915431
1	0.2	8.455652
1	0.3	10.989413
1	0.4	12.786772
1	0.5	14.045507

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()