Role of cytochrome P450 enzymes in drug-drug interactions.
Role of cytochrome P450 enzymes in drug-drug interactions.
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DOI：
10.1016/s1054-3589(08)60200-8
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发表时间：
1997-01-01
期刊：
影响因子：
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通讯作者：
Guengerich, F P
中科院分区：
文献类型：
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作者：
Guengerich, F P
许多不良的药物相互作用可归因于药代动力学问题，并且可以根据P450催化反应的改变来理解。现在对人类P450酶及其作用已经有了很多了解，并且有可能将这些信息应用于与实际问题相关的问题。人类P450总数中的一个相对较小的子集似乎负责大部分药物的氧化。涉及P450的药物相互作用的三个主要原因是诱导、抑制和可能的刺激，其中抑制似乎是已知临床问题中最重要的。利用人类P450和试剂的现有知识，可以用药物进行体外实验并做出有用的预测。结果可以在体内测试，再次使用基于我们对人类P450的了解的测定。这种方法不仅能够提高预测哪些药物可能会出现严重的相互作用问题，而且还可以减少必须进行的体内相互作用研究的数量。这些方法应随着进一步的完善和技术进步而得到改进。
Many adverse drug-drug interactions are attributable to pharmacokinetic problems and can be understood in terms of alterations of P450-catalyzed reactions. Much is now known about the human P450 enzymes and what they do, and it has been possible to apply this information to issues related to practical problems. A relatively small subset of the total number of human P450s appears to be responsible for a large fraction of the oxidation of drugs. The three major reasons for drug-drug interactions involving the P450s are induction, inhibition, and possibly stimulation, with inhibition appearing to be the most important in terms of known clinical problems. With the available knowledge of human P450s and reagents, it is possible to do in vitro experiments with drugs and make useful predictions. The results can be tested in vivo, again using assays based on our knowledge of human P450s. This approach has the capability of not only improving predictions about which drugs might show serious interaction problems, but also decreasing the number of in vivo interaction studies that must be performed. These approaches should improve with further refinement and technical advances.