Lin J H
Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
Drug Metab Dispos. 1998 Dec;26(12):1202-12.
The search for new drugs is an extremely time-consuming and costly endeavor. Much of the time and cost are expended on generating data that support the efficacy and safety profiles of the drug. Because of ethical constraints, relevant pharmacological and toxicological assessments must be made in laboratory animals and in in vitro systems before human testing can begin. In support of the efficacy and safety evaluation during drug development, two fundamental challenges facing industrial drug metabolism scientists are (1) how to "scale-up" the pharmacokinetic data from animals to humans and (2) how to extrapolate the in vitro data to the in vivo situation. This review examines the applications and limitations of interspecies scaling and in vitro extrapolation in pharmacokinetics.
寻找新药是一项极其耗时且成本高昂的工作。大部分时间和成本都花在生成支持药物疗效和安全性的数据上。由于伦理限制，在人体试验开始之前，必须在实验动物和体外系统中进行相关的药理学和毒理学评估。为了支持药物开发过程中的疗效和安全性评估，药物代谢领域的工业科学家面临的两个基本挑战是：（1）如何将动物的药代动力学数据“放大”到人类；（2）如何将体外数据外推到体内情况。本综述探讨了种间标度和体外外推在药代动力学中的应用及局限性。
