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Implications of Cytochrome P450 2C9 Polymorphism on Warfarin Metabolism and Dosing
Author(s) -
Redman Andrea R.
Publication year - 2001
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.21.2.235.34106
Subject(s) - cyp2c9 , warfarin , pharmacology , metabolism , cytochrome p450 , vitamin k epoxide reductase , dosing , isozyme , drug metabolism , biology , medicine , chemistry , biochemistry , enzyme , atrial fibrillation
Warfarin is an anticoagulant available as a racemic mixture. The R‐ and S‐isomers differ with respect to relative plasma concentrations, clearance, potency, sites of metabolism, and cytochrome P450 (CYP) isoenzymes responsible for metabolism. S‐Warfarin, the more potent isomer, is metabolized primarily by CYP2C9. Genetic polymorphisms resulting from single amino acid substitutions reduce the metabolic capability of 2C9. A reduction in warfarin metabolism due to genetic polymorphism may explain the increased warfarin response and bleeding episodes in some patients. Clinical studies showed an increased plasma level of S‐warfarin, decreased clearance of S‐warfarin, increased frequency of bleeding, and prolongation of hospitalization in patients with variant CYP2C9 alleles. Adverse outcomes associated with warfarin possibly could be avoided by identifying patients with variant alleles before therapy and starting therapy at low dosages.