Publication date: February 28th, 3:30 PM

PBPK Modeling to Simulate the Fate of Compounds in Living Organisms

Frédéric Y. Bois, Cleo Tebby, Céline Brochot

• In Silico Methods for Predicting Drug Toxicity pp 29-56

Abstract

Pharmacokinetics study the fate of xenobiotics in a living organism. Physiologically based pharmacokinetic (PBPK) models provide realistic descriptions of xenobiotics’ absorption, distribution, metabolism, and excretion processes. They model the body as a set of homogeneous compartments representing organs, and their parameters refer to anatomical, physiological, biochemical, and physicochemical entities. They offer a quantitative mechanistic framework to understand and simulate the time-course of the concentration of a substance in various organs and body fluids. These models are well suited for performing extrapolations inherent to toxicology and pharmacology (e.g., between species or doses) and for integrating data obtained from various sources (e.g., in vitro or in vivo experiments, structure–activity models). In this chapter, we describe the practical development and basic use of a PBPK model from model building to model simulations, through implementation with an easily accessible free software.

Key words

1,3-Butadiene PBPK Monte Carlo simulations Numerical integration R software