Tatsumi Akitoshi, Ikegami Yuki, Morii Ryoko, Sugiyama Masatoshi, Kadobayashi Muneo, Iwakawa Seigo
Educational Center for Clinical Pharmacy, Kobe Pharmaceutical University, Japan.
Biol Pharm Bull. 2009 Mar;32(3):517-9. doi: 10.1248/bpb.32.517.
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 mM) 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 mM) ethanol. Ethanol at a concentration of 3.0 vol% (510 mM) 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.
研究了乙醇对重组细胞色素P450 2C9.1微粒体（CYP2C9.1）代谢S-华法林和双氯芬酸的影响。低至0.1体积%（17 mM）的乙醇即可抑制S-华法林的7-羟基化代谢。乙醇以浓度依赖性方式降低S-华法林代谢的V(max)/K(m)和V(max)值，但乙醇对K(m)值无影响。即使在1.0体积%（170 mM）乙醇浓度下，也未观察到乙醇对双氯芬酸4'-羟基化代谢的抑制作用。浓度为3.0体积%（510 mM）的乙醇增加了双氯芬酸代谢的K(m)值，而V(max)未改变，这表明乙醇竞争性抑制了CYP2C9.1介导的双氯芬酸4'-羟基化。CYP2C9.1对S-华法林的代谢比对双氯芬酸的代谢对乙醇更敏感。这些结果表明，乙醇以底物依赖性方式抑制CYP2C9.1的代谢。
