title: Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes.
abstract: Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han-Chinese patients without prior warfarin treatments. Using the genotype-based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR > 4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R(2) of 0.62). This study demonstrated that pharmacogenetics-based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.
authors.affiliation: Department of Internal Medicine, Section of Cardiology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: M-S
authors.initials: MS
authors.lastname: Wen
authors.forename: Mtm
authors.initials: M
authors.lastname: Lee
authors.forename: J-J
authors.initials: JJ
authors.lastname: Chen
authors.forename: H-P
authors.initials: HP
authors.lastname: Chuang
authors.forename: L-S
authors.initials: LS
authors.lastname: Lu
authors.forename: C-H
authors.initials: CH
authors.lastname: Chen
authors.forename: T-H
authors.initials: TH
authors.lastname: Lee
authors.forename: C-T
authors.initials: CT
authors.lastname: Kuo
authors.forename: F-M
authors.initials: FM
authors.lastname: Sun
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Chang
authors.forename: P-L
authors.initials: PL
authors.lastname: Kuan
authors.forename: Y-F
authors.initials: YF
authors.lastname: Chen
authors.forename: M-J
authors.initials: MJ
authors.lastname: Charng
authors.forename: C-Y
authors.initials: CY
authors.lastname: Ray
authors.forename: J-Y
authors.initials: JY
authors.lastname: Wu
authors.forename: Y-T
authors.initials: YT
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000097:blood
chemical_list: D014859:Warfarin; 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