title: Influence of CYP2C9 and vitamin k oxide reductase complex (VKORC)1 polymorphisms on time to determine the warfarin maintenance dose.
abstract: Polymorphisms in cytochrome P450 (CYP) 2C9 and the vitamin K oxide reductase complex subunit 1 (VKORC1) greatly affect the maintenance dose of warfarin. To prevent adverse events, immediate dose adjustment is required. The purpose of this study was to investigate the influence of these polymorphisms on the time taken to determine the warfarin maintenance dose for individual patients, and to assess the advantages of genotype-based dosing on initial anticoagulant therapy. We analyzed the genotypes of CYP2C9 and VKORC1 from 72 patients. The number of days taken to determine the maintenance dose was compared with the genotypes. The time taken to determine the maintenance dose of warfarin in group A (CYP2C9*1/*1, VKORC1 -1639AA), B (*1/*1, - 1639GA), C (*1/*3, - 1639AA), and D (*1/*3, - 1639GA) patients was 19 +/- 19, 28 +/- 28, 27 +/- 20 and 7 days, respectively. We analyzed the relationship between the initial dose of warfarin and the number of days required to determine the maintenance dose based on the VKORC1 genotypes. Patients with the VKORC1 - 1639AA genotype and who were initially treated with more than 3mg warfarin, required approximately 2 weeks for the maintenance dose to be determined. Patients with the VKORC1 - 1639GA genotype and the same initial warfarin dosage required approximately a month; however, patients initially treated with 5 mg of warfarin only required 9.5 +/- 5.3 days. We found a tendency that the time taken to determine the warfarin maintenance dose depends on the genotypes. Genotype-based dosing may improve initial anticoagulant therapy.
authors.affiliation: Department of Pharmacy, Gunma University Hospital, Maebashi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Aomori
authors.forename: K
authors.initials: K
authors.lastname: Obayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Fujita
authors.forename: T
authors.initials: T
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Kurabayashi
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9; D004247:DNA / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D004247:DNA; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases