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标题：Effect of Ethanol on S-Warfarin and Diclofenac Metabolism by Recombinant Human CYP2C9.1
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作者：Akitoshi Tatsumi ; Yuki Ikegami ; Ryoko Morii 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：3
页码：517-519
DOI：10.1248/bpb.32.517
出版社：The Pharmaceutical Society of Japan
摘要：The effect of ethanol on the metabolism of S -warfarin and diclofenac by recombinant cytochrome P450 2C9.1 microsomes (CYP2C9.1) was studied. The 7-hydroxylation metabolism of S -warfarin was inhibited by as low as 0.1 vol% (17 m M ) ethanol. Ethanol decreased the V _max/ K _m and V _max values of S -warfarin metabolism in a concentration-dependent manner, but the K _m value was unchanged by ethanol. The inhibitory effect of ethanol on the 4′-hydroxylation metabolism of diclofenac was not observed even at 1.0 vol% (170 m M ) ethanol. Ethanol at a concentration of 3.0 vol% (510 m M ) increased the K _m value of diclofenac metabolism without changes in the V _max, which indicates that diclofenac 4′-hydroxylation by CYP2C9.1 was competitively inhibited by ethanol. S -Warfarin metabolism by CYP2C9.1 was more sensitive to ethanol than diclofenac metabolism. These results suggest that ethanol inhibits the metabolism by CYP2C9.1 in a substrate-dependent manner.
关键词：warfarin;ethanol;cytochrome P450 2C9.1 microsome;diclofenac;drug interaction;metabolism