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.
