cptpsp-tutorial-2019

Layout:

• Model files are under model:
  • Voriconazole PBPK model voriPBPK.cpp
  • Extended voriconazole PBPK model voriPBPK_ext.cpp
  • MAPK QSP model mapkQSP.cpp
• Digitized observed data are under data:
  • Observed voriconazole data for adult IV Adult_IV.csv, Pediatric IV Pediatric_IV.csv, adult oral Adult_PO.csv, and pediatric oral Pediatric_PO.csv https://www.ncbi.nlm.nih.gov/pubmed/25245942
  • Virtual population data s10vpop_pk.RDS for MAPK QSP model https://www.ncbi.nlm.nih.gov/pubmed/28649441
  • Tissue composition data tissue_comp_PT.csv for tissue:plasma partition coefficient calculation via the Poulin and Theil method https://www.ncbi.nlm.nih.gov/pubmed/11782904
• Scripts for running simulations and reproducing manuscript figures are under script

To reproduce manuscript figures:

1. Make the folder: script your working directory
2. Run pkgSetup.R to install required packages
3. To reproduce the plot in Figure 1, run mrgsolveIntro_script.R
4. To reproduce Figure 3, run voriPBPK_script.R
5. To reproduce Figure 5, run mapkQSP_script.R

Voriconazole PBPK model extension:

To better capture oral voriconazole PK, an extension to the original model was added to include a mechanistic absorption model with an intestinal clearance component. The permeability was optimized and the intestinal clearance was scaled from hepatic clearance guided by relative enzyme expression data https://www.jstage.jst.go.jp/article/yakushi/123/5/123_5_369/_article. The extended model is saved as voriPBPK_ext.cpp and the script to run the oral voriconazole simulations is voriPBPK_ext_script.R.