Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes.

Published

Journal 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 (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.

Full Text

Duke Authors

Cited Authors

  • Wen, M-S; Lee, M; 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

Published Date

  • July 2008

Published In

Volume / Issue

  • 84 / 1

Start / End Page

  • 83 - 89

PubMed ID

  • 18183038

Pubmed Central ID

  • 18183038

Electronic International Standard Serial Number (EISSN)

  • 1532-6535

Digital Object Identifier (DOI)

  • 10.1038/sj.clpt.6100453

Language

  • eng

Conference Location

  • United States