PBPK modelling of inter-individual variability in the pharmacokinetics of environmental chemicals

Frédéric Y. Bois (1, 2) , Massoud Jamei (3) , Harvey J. Clewell (4)

1 Math Modelling Syst Toxicol
2 INERIS - Institut National de l'Environnement Industriel et des Risques
3 SimCYP Ltd
4 The Hamner Institutes For Health Sciences

Generic PBPK models, applicable to a large number of substances, coupled to parameter databases and QSAR modules, are now available for predictive modelling of inter-individual variability in the absorption, distribution, metabolism and excretion of environmental chemicals. When needed, Markov chain Monte Carlo methods and multilevel population models can be jointly used for a Bayesian calibration of a PBPK model, to improve our understanding of the determinants of population heterogeneity and differential susceptibility. This article reviews those developments and illustrates them with recent applications to environmentally relevant questions.

Mots clés: DRUG-DRUG INTERACTIONS; MONTE CARLO SIMULATIONS; PBPK MODELS; POPULATION MODELS; SUSCEPTIBLE POPULATIONS; TOXICOKINETICS

Domaines: Toxicologie; Sciences de l'environnement

Frédéric Y. Bois, Massoud Jamei, Harvey J. Clewell. PBPK modelling of inter-individual variability in the pharmacokinetics of environmental chemicals. Toxicology, 2010, 278 (3), pp.256-267. ⟨10.1016/j.tox.2010.06.007⟩. ⟨ineris-00961755⟩