Pharmacogenomics and the management of oral anticoagulation.
Warfarin, the principal oral anticoagulant used in the treatment and prevention of thromboembolic disease, is primarily metabolized by CYP2C9, one of the hepatic microsomal enzymes. Recent advances in the field of pharmacogenomics have identified the gene responsible for encoding CYP2C9, as well as several mutations that are associated with decreased warfarin metabolism. Clinically, patients with these mutations are more sensitive to the effects of warfarin, require lower warfarin dosing requirements to reach a particular therapeutic endpoint, and are at increased risk for over-anticoagulation and bleeding complications during both initiation and maintenance therapy. Routine pharmacogenomic screening has not yet been applied to clinical practice or analyzed for cost effectiveness but may be useful in identifying patients at risk for warfarin-related complications.
Wittkowsky
Ann K
AK
University of Washington Medical Center, 1959 NE Pacific Street, Room BB112, Box 356015, Seattle, WA 98195, USA. akwitt@u.washington.edu
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology; D010597:Pharmacogenetics / Q000639:trends*; D014859:Warfarin / Q000493:pharmacokinetics / Q000627:therapeutic use
D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases