Educational PBPK

This physiologically based pharmacokinetic (PBPK) model is designed as an educational tool. The aim is to provide a simple, open source, freely downloadable PBPK model for performing basic single subject bottom-up simulations in R. The model has not been tested against a large set of compounds. All parameters were taken from the literature. The PBPK model was implemented by using the rxode2 package and non-compartmental analysis (NCA) was performed with the PKNCA package.

A running version of the app che be found here: https://manchester.shinyapps.io/pbpk/.

Additions, suggestions and amendments are welcome.

Files

• server.R: Shiny server function, it contains the "logics" of the applications (e.g., what happens when clicking a button).
• ui.R: Shiny user interface function, it contains the visual aspect of the application.
• main_pbpk_acat.R: R script that can be used to run the model outside the Shiny app. This file is not used in server.R or ui.R.
• functions/PBPK_model_rxode.R: it contains the ordinary differential equations of the PBPK and compartmental absorption & transit (CAT) models, written in RxODE format.
• functions/import_param.R: it contains the functions used to import and elaborate the PBPK and CAT model parameters.
• functions/functions_plot4.R: it contains the functions used to generate the plots.
• data/PBPK_parameters: it contains .xlsx files of the physiological parameters for all the species supported by the Manchester PBPK app. All the references are included in the .xlsx files.
• data/library_drugs:it contains .xlsx files of the drug physicochemical parameters and of drugs pharmacokinetics. All the references are included in the .xlsx files and in data/library_drugs/readme.txt.

How to install on a local machine

1. Install R (https://www.r-project.org/).
2. Install RStudio (https://www.rstudio.com/).
3. Open RStudio.
4. Install all libraries: copy, paste and run the following R code in the RStudio console or in a script.

install.packages(c("shiny","shinyBS","shinyjs","readxl","writexl","rxode2","dplyr","ggplot2","RColorBrewer","gridExtra","PKNCA","shinybusy"))

5. Restart RStudio.
6. Open server.R: double click on the file and it should open automatically.
7. Click on the green button "Run App" to run the app (It may crash on first use after installing all libraries so please try again).