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

Clin Pharmacol Ther. 2008 Jul;84(1):83-9. doi: 10.1038/sj.clpt.6100453. Epub 2008 Jan 9.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aryl Hydrocarbon Hydroxylases / blood
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Cytochrome P-450 CYP2C9
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / blood
  • Mixed Function Oxygenases / genetics*
  • Polymorphism, Genetic / genetics
  • Prospective Studies
  • Vitamin K Epoxide Reductases
  • Warfarin / administration & dosage*
  • Warfarin / blood

Substances

  • Warfarin
  • Mixed Function Oxygenases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases