Implementaton of Literature-Reported QSP Models in mrgsolve
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README.md

Translating literature-reported quantitative pharmacology models for simulation and interactive visualization

  • 20 July 2017 Cambridge Innovation Center, Cambridge MA
  • Presentation slide deck: index.pdf

References

The goal of this presentation was to translate and use models reported in the literature. Accordingly, we note that we were not involved in developing any of the models presented here, but acknowledge the authors who not only did the scientific work, but published that work in a way that allowed us to both read about and use their models.

Population Pharmacokinetic and Pharmacodynamic Model- Based Comparability Assessment of a Recombinant Human Epoetin Alfa and the Biosimilar HX575

Quantitative Analyses of Hepatic OATP-Mediated Interactions Between Statins and Inhibitors Using PBPK Modeling With a Parameter Optimization Method

Clinical responses to ERK inhibition in BRAF{V600E}-mutant colorectal cancer predicted using a computational model

Examples

EPO PK/PD model (Yan et al.) [code]

mod <- mread("epo", "content/model")

QW dosing is equally effective as TIW dosing for SC but not IV administration

  • EPOi = epo concentration (mIU/mL)
  • HGBi = hemoglobin (g/dL)

SC dosing

tiw <- ev_days(ev(amt=7800,ID=1,rate=-2), days="m,w,f", addl=3)
qw <- filter(tiw, time==0) %>% mutate(amt=40000,ID=2)

data_sc <- bind_rows(tiw,qw)

mod %>% zero_re %>% mrgsim(data=data_sc, end=700, delta=0.5) %>% 
  plot(EPOi+HGBi~time)

IV dosing

data_iv <- mutate(data_sc, rate=0, cmt=2)

mod %>% zero_re %>% mrgsim(data=data_iv, end=700, delta=0.5) %>% 
  plot(EPOi+HGBi~time)

OATP-DDI model (Yoshikado et al.) [code]

mod <- mread("yoshikado", "content/model")

Simulate the DDI between pitavastatin and cyclosporine

ddi <- c(ev(amt=2000, cmt=2),
         ev(amt=30,   cmt=1))

ddi <- as.data.frame(ddi) %>% mutate(ID=2)
no_ddi <- filter(ddi, amt==30) %>% mutate(ID=1)

data <- bind_rows(no_ddi,ddi)

out <- mod %>% mrgsim(data=data,end=14, delta=0.1)

Plot (code not shown)

ERK inhibition in CRC (Kirouac et al.) [code]

mod <- mread("mapk", "content/model")
vp <- read.csv("content/data/s10vpop.csv", header=TRUE) %>% slice(1)
mod <- param(mod,vp) %>% init(vp)

Simulate two cycles of GDC-0994 dosing

data <- expand.ev(amt=400, cmt=12, time=c(0,28), ii=1, addl=20) %>% mutate(ID=1)

out <- mrgsim(mod, data=data, end=56, delta=0.1, Req="GDC,TUMOR")

Plot (code not shown)

Implementation details

R packages

  • dplyr
  • readr
  • MCMCpack
  • minqa
  • tidyr
  • ggplot2
  • purrr
  • purrlyr
  • mrgsolvetk
  • dmutate

Special installation instructions

Please be sure to install mrgsolve, dmutate and mrgsolvetk from GitHub:

devtools::install_github("metrumresearchgroup/mrgsolve")
devtools::install_github("mrgsolve/mrgsolvetk")
devtools::install_github("kylebmetrum/dmutate")