Impact of Partition Coefficient Prediction Methods on PBPK Output Manuscript

Layout:

• PBPK model files are under model:
  • Alfentanil model alfentanilPBPK_Adult.cpp
  • Artemether model artemetherPBPK_adult.cpp
  • Caffeine model caffeinePBPK_adult.cpp
  • Digoxin model digoxinPBPK_Adult.cpp
  • Metoprolol model metoprololPBPK_Adult.cpp
  • Midazolam model midazolamPBPK_Adult.cpp
  • Nevirapine model nevirapinePBPK_Adult.cpp
  • Nifedipine model nifedipinePBPK_Adult.cpp
  • Ofloxacin model ofloxacinPBPK_Adult.cpp
  • Thiopental model thiopentalPBPK_Adult.cpp
  • Voriconazole model voriPBPK.cpp
• Digitized observed data are under data:
  • Observed alfentanil data obs_alfentanil.csv
  • Observed artemether data obs_artemether.csv
  • Observed caffeine data obs_caffeine.csv
  • Observed digoxin data obs_iv_digoxin.csv
  • Observed metoprolol data obs_metoprolol.csv
  • Observed midazolam data obs_midazolam.csv
  • Observed nevirapine data obs_nevirapine.csv
  • Observed nifedipine data obs_nifedipine.csv
  • Observed ofloxacin data obs_iv_ofloxacin.csv
  • Observed S-thiopental data obs_thiopental.csv
  • Observed R-thiopental data obs_thiopental_R.csv
  • Observed voriconazole data obs_voriconazole.csv
• Tissue composition data are under data:
  • Poulin and Theil tissue_comp_P&T.csv
  • Rodgers and Rowland tissue_comp_R&R.csv
  • Schmitt tissue_comp_Schmitt.csv
  • PK-Sim default PKSim_tissue_comp_pksim.csv
  • Standardized tissue composition unified_tissue_comp.csv
• Scripts for calculating tissue:plasma partition coefficients are under script:
  • Poulin and Theil CalcKp_P&T.R
  • Poulin and Theil Vss (used in verification) CalcVss_P&T.R
  • Berezhkovskiy CalcKp_Berez.R
  • Rodgers and Rowland CalcKp_R&R.R
  • Rodgers and Rowland Kpu (used in verification) CalcKpu_R&R.R
  • Schmitt CalcKp_Schmitt.R
  • PK-Sim default CalcKp_pksim.R
• Scripts for running simulations are under script:
  • Alfentanil simulation PBPK_sim_alfentanil.R
  • Artemether simulation PBPK_sim_artemether.R
  • Caffeine simulation PBPK_sim_caffeine.R
  • Digoxin simulation PBPK_sim_digoxin.R
  • Metoprolol simulation PBPK_sim_metoprolol.R
  • Midazolam simulation PBPK_sim_midazolam.R
  • Nevirapine simulation PBPK_sim_nevirapine.R
  • Nifedipine simulation PBPK_sim_nifedipine.R
  • Ofloxacin simulation PBPK_sim_ofloxacin.R
  • Thiopental simulation PBPK_sim_thiopental.R
  • Voriconazole simulation PBPK_sim_voriconazole.R
• Script for reproducting manuscript figures is under script

To reproduce manuscript figures:

1. Make the folder: script your working directory
2. Run pkgSetup.R to install required packages
3. Run each section of script.R to reproduce Figures 2-7 and Table 2

Update (April 25, 2022):

CalcKp_Schmitt.R was updated to correct a typo in the calculation of K_n_l for diprotic bases.

Update (January 26, 2023):

CalcKp_R&R.R was updated to correct a typo in the calculation of Kpu_bc, which impacts the calculation of Kp values for moderate to strong bases.