Effect of ethanol on S-warfarin and diclofenac metabolism by recombinant human CYP2C9.1.
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Tatsumi A, Ikegami Y, Morii R, Sugiyama M, Kadobayashi M, Iwakawa S
Effect of ethanol on S-warfarin and diclofenac metabolism by recombinant human CYP2C9.1.
Biol Pharm Bull. 2009 Mar;32(3):517-9.
- PubMed ID
- 19252308 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Ethanol Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails - Drug Interactions
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