Abstract:
: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.
journal_name
Pharmacotherapyjournal_title
Pharmacotherapyauthors
Redman ARdoi
10.1592/phco.21.2.235.34106subject
Has Abstractpub_date
2001-02-01 00:00:00pages
235-42issue
2eissn
0277-0008issn
1875-9114journal_volume
21pub_type
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