Premium
Combination of Phenotype Assessments and CYP2C9‐VKORC1 Polymorphisms in the Determination of Warfarin Dose Requirements in Heavily Medicated Patients
Author(s) -
Michaud V,
Vanier MC,
Brouillette D,
Roy D,
Verret L,
Noel N,
Taillon I,
O‧Hara G,
Gossard D,
Champagne M,
Goodman K,
Renaud Y,
Brown A,
Phillips M,
Ajami AM,
Turgeon J
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100434
Subject(s) - vkorc1 , warfarin , vitamin k epoxide reductase , cyp2c9 , medicine , pharmacology , genotype , losartan , biology , genetics , gene , atrial fibrillation , cytochrome p450 , renin–angiotensin system , blood pressure , metabolism
The relative contribution of phenotypic measures and CYP2C9 ‐vitamin K epoxide reductase complex subunit 1 ( VKORC1 ) polymorphisms to warfarin dose requirements at day 14 was determined in 132 hospitalized, heavily medicated patients. Phenotypic measures were (1) the urinary losartan metabolic ratio before the first dose of warfarin, (2) the S : R ‐warfarin ratio at day 1, and (3) a dose‐adjusted international normalized ratio (INR) at day 4. CYP2C9 and VKORC1 genotypes were determined by gene chip analysis. In multivariate analyses, the dose‐adjusted INR at day 4 explained 31% of variability observed in warfarin doses at day 14, whereas genotypic measures ( CYP2C9 ‐ VKORC1 ) contributed 6.5%. When S : R ‐warfarin ratio was used, genotypes contributed more significantly (23.5%). Finally, urinary losartan metabolic ratio was of low predictive value. The best models obtained explained 51% of intersubject variability in warfarin dose requirements. Thus, combination of a phenotypic measure to CYP2C9‐VKORC1 genotypes represents a useful strategy to predict warfarin doses in patients receiving multiple drugs (11±4 drugs/day). Clinical Pharmacology & Therapeutics (2008); 83 , 5, 740–748. doi: 10.1038/sj.clpt.6100434