Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients: highlighting the importance of population-specific calibration

Pharmacogenomics. 2015 Jul;16(8):865-76. doi: 10.2217/pgs.15.48. Epub 2015 Jun 8.

Abstract

Background: The main aims of the present study were to develop a pharmacogenetic-based warfarin dosing algorithm and to validate it in a highly admixed population.

Materials & methods: We included two patient cohorts treated with warfarin (first cohort, n = 832; and second cohort, n = 133).

Results: Our algorithm achieved a determination coefficient of 40% including the variables age, gender, weight, height, self-declared race, amiodarone use, enzyme inducers use, VKORC1 genotypes and predicted phenotypes according to CYP2C9 polymorphisms.

Conclusion: Data suggest that our developed algorithm is more accurate than the IWPC algorithm when the application is focused on patients from the Brazilian population. Population-specific derivation and/or calibration of warfarin dosing algorithms may lead to improved performance compared with general use dosing algorithms currently available. Original submitted 26 November 2014; Revision submitted 9 April 2015.

Keywords: CYP2C9; VKORC; algorithm; warfarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticoagulants / administration & dosage*
  • Brazil
  • Calibration
  • Cytochrome P-450 CYP2C9 / genetics*
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Phenotype
  • Vitamin K Epoxide Reductases / genetics*
  • Warfarin / administration & dosage*

Substances

  • Anticoagulants
  • Warfarin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases