Physiologically based approaches towards the prediction of pharmacokinetics: in vitro-in vivo extrapolation.
In adapting to the challenge to make more informed selection of compounds for development, the pharmaceutical industry is increasingly embracing the application of mechanism-based models and prediction tools for prediction of pharmacokinetic parameters. This review first outlines the concepts and application of the major physiologically based prediction tools to extrapolate clearance, tissue distribution, and rate and extent of absorption from minimal in vitro or animal in vivo input data. Finally, the ability of these prediction tools, when placed within a generic whole body physiologically based model of pharmacokinetics, to predict plasma concentration-time profiles is briefly discussed.
De Buck
Stefan S
SS
Johnson & Johnson Pharmaceutical Research and Development, Division of Janssen Pharmaceutica N.V., Discovery ADME-Tox, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Mackie
Claire E
CE
D000465:Algorithms; D000818:Animals; D004345:Drug Industry / Q000379:methods; D006801:Humans; D008657:Metabolic Clearance Rate; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D014018:Tissue Distribution
D004364:Pharmaceutical Preparations