Bois Frederic Y, Brochot Céline
INERIS, DRC/VIVA/METO, Parc ALATA, BP 2, 60550, Verneuil en Halatte, France.
Methods Mol Biol. 2016;1425:37-62. doi: 10.1007/978-1-4939-3609-0_3.
Pharmacokinetics is the study of 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.
药物动力学是研究异生物质在活生物体中的命运。基于生理的药物动力学（PBPK）模型提供了异生物质吸收、分布、代谢和排泄过程的真实描述。它们将身体建模为一组代表器官的均匀隔室，其参数涉及解剖学、生理学、生物化学和物理化学实体。它们提供了一个定量的机制框架，以理解和模拟物质在各种器官和体液中的浓度随时间变化的过程。这些模型非常适合进行毒理学和药理学固有的外推（例如，在物种或剂量之间），以及整合从各种来源获得的数据（例如，体外或体内实验、构效关系模型）。在本章中，我们将通过使用易于获取的免费软件进行实现，描述一个PBPK模型从模型构建到模型模拟的实际开发和基本使用。
