Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 84, Issue 1, Pages 83-89Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.clpt.6100453
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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.
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