Problems associated with in vitro assessment of drug inhibition of CYP3A4 and other P-450 enzymes and its impact on drug discovery

被引:17
作者
Wienkers, LC [1 ]
机构
[1] Pharmacia Corp, Kalamazoo, MI 49007 USA
关键词
drug inhibition; high throughput; drug discovery; cytochrome P-450;
D O I
10.1016/S1056-8719(01)00121-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The cytochromes P-450 recognize and metabolize a broad range of structurally diverse therapeutic agents. As a consequence, many clinically relevant drug-drug interactions (DDI) are associated with inhibition and/or induction of a specific P-450 enzymes (in particular human cytochrome P-450 3A4, CYP3A4). In addition to inhibition and induction, CYP-mediated drug metabolism may be enhanced upon coincubation with certain compounds. Moreover, some of these enzyme-based interactions appear to be substrate specific. In this presentation, several issues associated with the generation of accurate DDI information will be discussed. (C) 2001 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:79 / 84
页数:6
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