De Buck Stefan S, Mackie Claire E
Johnson & Johnson Pharmaceutical Research and Development, Division of Janssen Pharmaceutica N.V., Discovery ADME-Tox, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Expert Opin Drug Metab Toxicol. 2007 Dec;3(6):865-78. doi: 10.1517/17425255.3.6.865.
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.
为了应对在选择化合物进行开发时做出更明智决策的挑战，制药行业越来越多地采用基于机制的模型和预测工具来预测药代动力学参数。本综述首先概述了主要基于生理学的预测工具的概念和应用，以便从最少的体外或动物体内输入数据推断清除率、组织分布以及吸收速率和程度。最后，简要讨论了这些预测工具在通用的基于生理学的全身药代动力学模型中预测血浆浓度-时间曲线的能力。
