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Wen, M‐S; Lee, MTM; Chen, J‐J; Chuang, H‐P; Lu, L‐S; Chen, C‐H; Lee, T‐H; Kuo, C‐T; Sun, F‐M; Chang, Y‐J; Kuan, P‐L; Chen, Y‐F; Charng, M‐J; Ray, C‐Y; Wu, J‐Y; Chen, Y‐T
Clinical pharmacology and therapeutics, July 2008, Volume: 84, Issue: 1Journal Article
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 (R2 of 0.62). This study demonstrated that pharmacogenetics‐based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity. Clinical Pharmacology & Therapeutics (2008); 84, 1, 83–89 doi:10.1038/sj.clpt.6100453
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