Verification of five pharmacogenomics-based warfarin administration models

Indian J Pharmacol. 2016 May-Jun;48(3):258-63. doi: 10.4103/0253-7613.182876.

Abstract

Objective: This study aims to screen and validate five individual warfarin dosing models (four Asian model algorithms, namely, Ohno, Wen, Miao, Huang, and the algorithm of International Warfarin Pharmacogenetic Consortium, namely IWPC algorithm) with the aim of evaluating their accuracy, practicality, and safety.

Materials and methods: Patients' CYP2C9*3 and VKORC1-1639G >A genes were genotyped, and patient-related information and steady warfarin doses were recorded. The difference between the predicted dose and actual maintenance dose of each model was compared.

Results: The prediction accuracies of the Huang and Wen models were the highest. In terms of clinical practicality, the Huang model rated the highest for the low-dose group, whereas the Ohno and IWPC models rated the highest for the middle-dose group. The models tended to markedly overpredict the doses in the low-dose group, especially the IWPC model. The Miao model tended to severely underpredict the doses in the middle-dose group, whereas no model exhibited severe overprediction.

Conclusions: Since none of the models ranked high for all the three criteria considered, the impact of various factors should be thoroughly considered before selecting the most appropriate model for the region's population.

Keywords: Mechanical heart valve replacement; model; pharmacogenomics; verification; warfarin.

Publication types

  • Validation Study

MeSH terms

  • Anticoagulants / administration & dosage*
  • Cytochrome P-450 CYP2C9 / metabolism
  • Humans
  • Models, Theoretical*
  • Pharmacogenetics*
  • Warfarin / administration & dosage*

Substances

  • Anticoagulants
  • Warfarin
  • Cytochrome P-450 CYP2C9