Role of pharmacokinetics in the discovery and development of indinavir

被引:40
作者
Lin, JH [1 ]
机构
[1] Merck Res Labs, W Point, PA 19486 USA
关键词
rational drug design; pH-dependent absorption; drug-drug interactions; P-glycoprotein; intestinal first-pass metabolism; prediction of hepatic clearance;
D O I
10.1016/S0169-409X(99)00018-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The discovery of indinavir is a successful example in which pharmacokinetic and metabolic information were incorporated into drug design. The use of animal and in vitro human metabolic data in predicting the oral bioavailability and hepatic clearance in humans was critical in selecting indinavir as a drug candidate for development. Ln its development stage, pharmncokinetics continued to play an important role in identifying the key properties of indinavir in vivo, which allowed the characterization and prediction of the time course of drug action under physiological and pathological conditions. This review describes the role of pharmacokinetics and drug metabolism in the discovery and development of indinavir. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:33 / 49
页数:17
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