Combination of Phenotype Assessments and CYP2C9-VKORC1 Polymorphisms in the Determination of Warfarin Dose Requirements in Heavily Medicated Patients
| Autor: | Nicolas Noël, Jacques Turgeon, G O‧Hara, Y Renaud, Denis Brouillette, Michael S. Phillips, Denis-Claude Roy, M‐C Vanier, Denis Gossard, I. Taillon, AM Ajami, K Goodman, Veronique Michaud, Lucie Verret, Andrew M.K. Brown, Martin A. Champagne |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Multivariate analysis medicine.drug_class Biology Pharmacology Polymorphism Single Nucleotide Mixed Function Oxygenases Vitamin K Epoxide Reductases Atrial Fibrillation medicine Humans heterocyclic compounds Pharmacology (medical) cardiovascular diseases CYP2C9 Aged Cytochrome P-450 CYP2C9 Aged 80 and over Dose-Response Relationship Drug Anticoagulant Warfarin Anticoagulants Middle Aged Vitamin-K-epoxide reductase (warfarin-sensitive) Phenotype Losartan Regression Analysis Vitamin K epoxide reductase Aryl Hydrocarbon Hydroxylases VKORC1 medicine.drug |
| Zdroj: | Clinical Pharmacology & Therapeutics. 83:740-748 |
| ISSN: | 1532-6535 0009-9236 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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