Contribution of three CYP3A isoforms to metabolism of R- and S-warfarin.
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Jones DR, Kim SY, Boysen G, Yun CH, Miller GP
Contribution of three CYP3A isoforms to metabolism of R- and S-warfarin.
Drug Metab Lett. 2010 Dec;4(4):213-9.
- PubMed ID
- 20615193 [ View in PubMed]
- Abstract
Effective coumadin (R/S-warfarin) therapy is complicated by inter-individual variability in metabolism. Recent studies have demonstrated that CYP3A isoforms likely contribute to patient responses and clinical outcomes. Despite a significant focus on CYP3A4, little is known about CYP3A5 and CYP3A7 metabolism of warfarin. Based on our studies, recombinant CYP3A4, CYP3A5 and CYP3A7 metabolized R- and S-warfarin to 10- and 4'-hydroxywarfarin with efficiencies that depended on the individual enzymes. For R-warfarin, CYP3A4, CYP3A7, and CYP3A5 demonstrated decreasing preference for 10-hydroxylation over 4'-hydroxylation. By contrast, there was no regioselectivity toward S-warfarin. While all enzymes preferentially metabolized R-warfarin, CYP3A4 was the most efficient at metabolizing all reactions. Individuals, namely African-Americans and children, with higher relative levels of CYP3A5 and/or CYP3A7, respectively, compared to CYP3A4 may metabolize warfarin less efficiently and thus may require lower doses and be at risk for adverse drug-drug interactions related to the contributions of the respective enzymes.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions (S)-Warfarin Cytochrome P450 3A4 Protein Humans NoSubstrateDetails - Drug Interactions
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