Department of Discovery DMPK, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE115RH, UK.
Mol Pharm. 2009 Nov-Dec;6(6):1662-77. doi: 10.1021/mp800246x.
The ability to predict hepatic metabolic clearance is a key component in the design and selection of small molecule drug candidates within the pharmaceutical industry. The recognition that metabolism-transporter interplay can influence hepatic metabolic clearance has presented new challenges, both in terms of the creation of experimental systems suitable for an industry setting and also in developing an understanding of the pharmacokinetic concepts that underpin them. This paper reviews the pharmacokinetic principles that govern the kinetics of uptake transporter substrates. In addition, new data are presented from a range of test systems for assessing hepatic drug clearance and the impact of drug-drug interactions (DDIs).
预测肝脏代谢清除率的能力是制药行业中小分子药物候选物设计和选择的关键组成部分。认识到代谢-转运体相互作用会影响肝脏代谢清除率，这在创建适合工业环境的实验系统以及开发理解其基础的药代动力学概念方面都带来了新的挑战。本文综述了控制摄取转运体底物动力学的药代动力学原则。此外，还从一系列用于评估肝脏药物清除率和药物-药物相互作用（DDI）影响的测试系统中呈现了新数据。
