pk-curves.R
In pmxTools: Pharmacometric and Pharmacokinetic Toolkit

## ---- include = FALSE---------------------------------------------------------
knitr::opts_chunk$set(
  collapse = TRUE,
  comment = "#>"
)

## ----setup, warning=F, message=F----------------------------------------------
library(pmxTools)
library(patchwork)

## ----1cptdemo, fig.height=10, fig.width=7,message=FALSE-----------------------

library(ggplot2)

t <- seq(0, 24, by=0.1)

df1 <- data.frame(t = t,
                  Cp1 = calc_sd_1cmt_linear_bolus(t = t, dose = 600, CL = 5, V = 20),
                  Cp2 = calc_sd_1cmt_linear_infusion(t = t, dose = 600, CL = 5, V = 20, tinf=2),
                  Cp3 = calc_sd_1cmt_linear_oral_0(t = t, dose = 600, CL = 5, V = 20, dur=2),
                  Cp4 = calc_sd_1cmt_linear_oral_0_lag(t = t, dose = 600, CL = 5, V = 20, dur=2, tlag=1),
                  Cp5 = calc_sd_1cmt_linear_oral_1(t = t, dose = 600, CL = 5, V = 20, ka=1.5),
                  Cp6 = calc_sd_1cmt_linear_oral_1_lag(t = t, dose = 600, CL = 5, V = 20, ka=1.5, tlag=1))

p1.1 <- ggplot(df1, aes(t, Cp1)) +
  geom_line() +
  labs(title="Bolus dose")

p1.2 <- ggplot(df1, aes(t, Cp2)) +
  geom_line() +
  labs(title="Infusion")

p1.3 <- ggplot(df1, aes(t, Cp3)) +
  geom_line() +
  labs(title="Zero-order oral")

p1.4 <- ggplot(df1, aes(t, Cp4)) +
  geom_line() +
  labs(title="Zero-order oral with lag time")

p1.5 <- ggplot(df1, aes(t, Cp5)) +
  geom_line() +
  labs(title="First-order oral")

p1.6 <- ggplot(df1, aes(t, Cp6)) +
  geom_line() +
  labs(title="First-order oral with lag time")

p1.1 + p1.2 + p1.3 + p1.4 + p1.5 + p1.6 + plot_layout(nrow=3)


## ----1cptssdemo, fig.height=10, fig.width=7,message=FALSE---------------------

t <- seq(0, 24, by=0.1)

df1ss <- data.frame(t = t,
                  Cp1 = calc_ss_1cmt_linear_bolus(t = t, tau = 24, dose = 600, CL = 1, V = 20),
                  Cp2 = calc_ss_1cmt_linear_infusion(t = t, tau = 24, dose = 600, CL = 1, V = 20, tinf=2),
                  Cp3 = calc_ss_1cmt_linear_oral_0(t = t, tau = 24, dose = 600, CL = 1, V = 20, dur=2),
                  Cp4 = calc_ss_1cmt_linear_oral_0_lag(t = t, tau = 24, dose = 600, CL = 1, V = 20, dur=2, tlag=1.5),
                  Cp5 = calc_ss_1cmt_linear_oral_1(t = t, tau = 24, dose = 600, CL = 1, V = 20, ka=1.5),
                  Cp6 = calc_ss_1cmt_linear_oral_1_lag(t = t, tau = 24, dose = 600, CL = 1, V = 20, ka=1.5, tlag=1.5))

p1.1ss <- ggplot(df1ss, aes(t, Cp1)) +
  geom_line() +
  labs(title="Bolus dose")

p1.2ss <- ggplot(df1ss, aes(t, Cp2)) +
  geom_line() +
  labs(title="Infusion")

p1.3ss <- ggplot(df1ss, aes(t, Cp3)) +
  geom_line() +
  labs(title="Zero-order oral")

p1.4ss <- ggplot(df1ss, aes(t, Cp4)) +
  geom_line() +
  labs(title="Zero-order oral with lag time")

p1.5ss <- ggplot(df1ss, aes(t, Cp5)) +
  geom_line() +
  labs(title="First-order oral")

p1.6ss <- ggplot(df1ss, aes(t, Cp6)) +
  geom_line() +
  labs(title="First-order oral with lag time")

p1.1ss + p1.2ss + p1.3ss + p1.4ss + p1.5ss + p1.6ss + plot_layout(nrow=3)


## ----2cptdemo, fig.height=10, fig.width=7, message=FALSE----------------------

t <- seq(0, 24, by=0.1)

df2 <- data.frame(t = t,
                  Cp1 = calc_sd_2cmt_linear_bolus(t = t, dose = 600, CL = 5, V1 = 20, V2 = 80, Q = 1),
                  Cp2 = calc_sd_2cmt_linear_infusion(t = t, dose = 600, CL = 5, V1 = 20, V2 = 80, Q = 1, tinf=2),
                  Cp3 = calc_sd_2cmt_linear_oral_0(t = t, dose = 600, CL = 5, V1 = 20, V2 = 80, Q = 1, dur=2),
                  Cp4 = calc_sd_2cmt_linear_oral_0_lag(t = t, dose = 600, CL = 5, V1 = 20, V2 = 80, Q = 1, dur=2, tlag=1),
                  Cp5 = calc_sd_2cmt_linear_oral_1(t = t, dose = 600, CL = 5, V1 = 20, V2 = 80, Q = 1, ka=1.5),
                  Cp6 = calc_sd_2cmt_linear_oral_1_lag(t = t, dose = 600, CL = 5, V1 = 20, V2 = 80, Q = 1, ka=1.5, tlag=1))

p2.1 <- ggplot(df2, aes(t, Cp1)) +
  geom_line() +
  labs(title="Bolus dose")

p2.2 <- ggplot(df2, aes(t, Cp2)) +
  geom_line() +
  labs(title="Infusion")

p2.3 <- ggplot(df2, aes(t, Cp3)) +
  geom_line() +
  labs(title="Zero-order oral")

p2.4 <- ggplot(df2, aes(t, Cp4)) +
  geom_line() +
  labs(title="Zero-order oral with lag time")

p2.5 <- ggplot(df2, aes(t, Cp5)) +
  geom_line() +
  labs(title="First-order oral")

p2.6 <- ggplot(df2, aes(t, Cp6)) +
  geom_line() +
  labs(title="First-order oral with lag time")

p2.1 + p2.2 + p2.3 + p2.4 + p2.5 + p2.6 + plot_layout(nrow=3)


## ----2cptssdemo, fig.height=10, fig.width=7,message=FALSE---------------------

t <- seq(0, 24, by=0.1)

df2ss <- data.frame(t = t,
                  Cp1 = calc_ss_2cmt_linear_bolus(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 80, Q = 0.25),
                  Cp2 = calc_ss_2cmt_linear_infusion(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 80, Q = 0.25, tinf=2),
                  Cp3 = calc_ss_2cmt_linear_oral_0(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 80, Q = 0.25, dur=2),
                  Cp4 = calc_ss_2cmt_linear_oral_0_lag(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 80, Q = 0.25, dur=2, tlag=1.5),
                  Cp5 = calc_ss_2cmt_linear_oral_1(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 80, Q = 0.25, ka=1.5),
                  Cp6 = calc_ss_2cmt_linear_oral_1_lag(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 80, Q = 0.25, ka=1.5, tlag=1.5))

p2.1ss <- ggplot(df2ss, aes(t, Cp1)) +
  geom_line() +
  labs(title="Bolus dose")

p2.2ss <- ggplot(df2ss, aes(t, Cp2)) +
  geom_line() +
  labs(title="Infusion")

p2.3ss <- ggplot(df2ss, aes(t, Cp3)) +
  geom_line() +
  labs(title="Zero-order oral")

p2.4ss <- ggplot(df2ss, aes(t, Cp4)) +
  geom_line() +
  labs(title="Zero-order oral with lag time")

p2.5ss <- ggplot(df2ss, aes(t, Cp5)) +
  geom_line() +
  labs(title="First-order oral")

p2.6ss <- ggplot(df2ss, aes(t, Cp6)) +
  geom_line() +
  labs(title="First-order oral with lag time")

p2.1ss + p2.2ss + p2.3ss + p2.4ss + p2.5ss + p2.6ss + plot_layout(nrow=3)


## ----3cptdemo, fig.height=10, fig.width=7, message=FALSE----------------------

t <- seq(0, 24, by=0.1)

df3 <- data.frame(t = t,
                  Cp1 = calc_sd_3cmt_linear_bolus(t = t, CL = 3.5, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, dose = 600),
                  Cp2 = calc_sd_3cmt_linear_infusion(t = t, CL = 3.5, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, dose = 600, tinf=2),
                  Cp3 = calc_sd_3cmt_linear_oral_0(t = t, CL = 3.5, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, dose = 600, dur=2),
                  Cp4 = calc_sd_3cmt_linear_oral_0_lag(t = t, CL = 3.5, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, dose = 600, dur=2, tlag=1),
                  Cp5 = calc_sd_3cmt_linear_oral_1(t = t, CL = 3.5, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, dose = 600, ka=1.5),
                  Cp6 = calc_sd_3cmt_linear_oral_1_lag(t = t, CL = 3.5, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, dose = 600, ka=1.5, tlag=1))

p3.1 <- ggplot(df3, aes(t, Cp1)) +
  geom_line() +
  labs(title="Bolus dose")

p3.2 <- ggplot(df3, aes(t, Cp2)) +
  geom_line() +
  labs(title="Infusion")

p3.3 <- ggplot(df3, aes(t, Cp3)) +
  geom_line() +
  labs(title="Zero-order oral")

p3.4 <- ggplot(df3, aes(t, Cp4)) +
  geom_line() +
  labs(title="Zero-order oral with lag time")

p3.5 <- ggplot(df3, aes(t, Cp5)) +
  geom_line() +
  labs(title="First-order oral")

p3.6 <- ggplot(df3, aes(t, Cp6)) +
  geom_line() +
  labs(title="First-order oral with lag time")

p3.1 + p3.2 + p3.3 + p3.4 + p3.5 + p3.6  + plot_layout(nrow=3)


## ----3cptssdemo, fig.height=10, fig.width=7,message=FALSE---------------------

t <- seq(0, 24, by=0.1)

df3ss <- data.frame(t = t,
                  Cp1 = calc_ss_3cmt_linear_bolus(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05),
                  Cp2 = calc_ss_3cmt_linear_infusion(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, tinf=2),
                  Cp3 = calc_ss_3cmt_linear_oral_0(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, dur=2),
                  Cp4 = calc_ss_3cmt_linear_oral_0_lag(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, dur=2, tlag=1.5),
                  Cp5 = calc_ss_3cmt_linear_oral_1(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, ka=1.5),
                  Cp6 = calc_ss_3cmt_linear_oral_1_lag(tad = t, tau = 24, dose = 600, CL = 1, V1 = 20, V2 = 500, V3 = 200, Q2 = 0.5, Q3 = 0.05, ka=1.5, tlag=1.5))

p3.1ss <- ggplot(df3ss, aes(t, Cp1)) +
  geom_line() +
  labs(title="Bolus dose")

p3.2ss <- ggplot(df3ss, aes(t, Cp2)) +
  geom_line() +
  labs(title="Infusion")

p3.3ss <- ggplot(df3ss, aes(t, Cp3)) +
  geom_line() +
  labs(title="Zero-order oral")

p3.4ss <- ggplot(df3ss, aes(t, Cp4)) +
  geom_line() +
  labs(title="Zero-order oral with lag time")

p3.5ss <- ggplot(df3ss, aes(t, Cp5)) +
  geom_line() +
  labs(title="First-order oral")

p3.6ss <- ggplot(df3ss, aes(t, Cp6)) +
  geom_line() +
  labs(title="First-order oral with lag time")

p3.1ss + p3.2ss + p3.3ss + p3.4ss + p3.5ss + p3.6ss  + plot_layout(nrow=3)

## ----pkcurve1, fig.height=4, fig.width=7,message=FALSE------------------------

dfcurve1 <- pk_curve(t=seq(0,168,by=0.1), model="3cmt_oral", ii=24, addl=12,
                     params=list(CL=1.5, V1=25, V2=2, V3=5, Q2=0.5, Q3=0.25, ka=1))

ggplot(dfcurve1, aes(t, cp)) +
  geom_line()