Author/Editor		Herman, D; Locatelli, I; Grabnar, I; Peternel, P; Stegnar, M; Mrhar, A; Breskvar, K; Dolžan, V
Title		Influence of CYP2C9 polymorphisms, demographic factors and concomitant drug therapy on warfarin metabolism and maintenance dose
Type		članek
Source		Pharmacogenomics J
Vol. and No.		Letnik 5
Publication year		2005
Volume		str. 193-202
Language		eng
Abstract		Warfarin is an anticoagulant drug with narrow therapeutic index and high interindividual variability in dose requirement. S-warfarin is metabolized mainly by polymorphic cytochrome P450 (CYP) 2C9. We systematically quantified the influence of CYP2C9 genotype, demographic factors and concomitant drug treatment on warfarin metabolism and maintenance dose. The mean warfarin doseswere lower in carriers of one (2.71 mg day, 59 patients) and two polymorphic alleles (1.64 mg day, 11 patients) than in carriers of two wild-type alleles (4.88 mg day, 118 patients). Multiple regression analysis demonstrated that CYP2C9 genotype, age, concomitant treatment with warfarin metabolism inducers and lean body weight contributed significantly to interindividual variability in warfarin dose requirement (adjusted R2=0.37). The same factors, except for age, significantly influenced S-warfarin clearance (adjusted R2=0.42). These results can serve as a starting point for designing prospective studies in patients in the initiation phase of genotype-based warfarin therapy.
Descriptors		THROMBOPHLEBITIS WARFARIN POLYMORPHISM (GENETICS) CYTOCHROME P-450 GENOTYPE ALLELES DOSE-RESPONSE RELATIONSHIP, DRUG REGRESSION ANALYSIS