SimBiology

Whole Body Physiologically-based Pharmacokinetic (PBPK) model

This document presents a SimBiology ® model of a generic whole - body physiologically - based pharmacokinetic (WB - PBPK) model as described in the article “Evaluation of a generic physiologically based pharmacokinet ic model for lineshape analysis” by Sheila Annie Peters [1]

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Model Description

The generic PBPK model presented here was originally developed by Sheila Annie Peters and used for lineshape analysis, to investigate clinical PK data by exploring the effects of additional or alternative absorption, distribution, metabolism, and excretion ( ADME ) pathways. The model includes an expanded version of the compartmental absorption and transit (CAT) model of gastrointestinal absorption, additionally including enterohepatic recycling, gut wall metabolism, and paracellular absorption. Tissue partition coefficients are calculated according to equations presented by Rodgers et al [2][3]. Drug parameters describing Atenolol and Captopril ADME are included as variants. Other variants packaged with this SimBiology project file describe Human fasted, Human fed and Rat physiologies and allow easy scale - up from Rat PK to Human PK. More information on the use of this model can be found in the Description section of the Model tab.

Whole Body Physiologically-based Pharmacokinetic (PBPK) model

References

[1] Peters, S. A. (2008). Evaluation of a generic physiologically based pharmacokinetic model for lineshape analysis. Clinical pharmacokinetics, 47(4), 261–75.

[2] Rodgers, T., Leahy, D., & Rowland, M. (2005). Physiologically Based Pharmacokinetic Modeling 1: Predicting the Tissue Distribution of Moderate-to-Strong Bases. Journal of Pharmaceutical Sciences, 94(6), 1259 – 76.

[3] Rodgers, T., & Rowland, M. (2006). Physiologically Based Pharmacokinetic Modeling 2: Predicting the Tissue Distribution of Acids, Very Weak Bases, Neutrals and Zwitterions. Journal of pharmaceutical sciences , 95(6), 1238 – 1257