title: Physiologically based pharmacokinetics (PBPK).
abstract: Allometric scaling is widely used to predict human pharmacokinetic parameters from preclinical species, and many different approaches have been proposed over the years to improve its predictive performance. Nevertheless, prediction errors are commonly observed in the practical application of simple allometry, for example, in cases where the hepatic metabolic clearance is mainly determined by enzyme activities, which do not scale allometrically across species. Therefore, if good correlation was noted for some drugs, poor correlation was observed for others, highlighting the need for other conceptual approaches. Physiologically based pharmacokinetic (PBPK) models are now a well-established approach to conduct extrapolations across species and to generate simulations of pharmacokinetic profiles under various physiological conditions. While conventional pharmacokinetic models are defined by drug-related data themselves, PBPK models have richer information content and integrate information from various sources, including drug-dependent, physiological, and biological parameters as they vary in between species, subjects, or with age and disease state. Therefore, the biological and mechanistic bases of PBPK models allow the extrapolation of the kinetic behavior of drugs with regard to dose, route, and species. In addition, by providing a link between tissue concentrations and toxicological or pharmacological effects, PBPK modeling represents a framework for mechanistic pharmacokinetic-pharmacodynamic models.
authors: UCB Pharma SA, Belgium.
authors: Pascal
authors: P
authors: Espié
authors: Dominique
authors: D
authors: Tytgat
authors: Maria-Laura
authors: ML
authors: Sargentini-Maier
authors: Italo
authors: I
authors: Poggesi
authors: Jean-Baptiste
authors: JB
authors: Watelet
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D003198:Computer Simulation; D055808:Drug Discovery; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D010599:Pharmacokinetics; D010827:Physiology; D015203:Reproducibility of Results; D013045:Species Specificity
chemical_list: D004364:Pharmaceutical Preparations