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- Title
Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin.
- Authors
Gage, B. F.; Eby, C.; Johnson, J. A.; Deych, E.; Rieder, M. J.; Ridker, P. M.; Milligan, P. E.; Grice, G.; Lenzini, P.; Rettie, A. E.; Aquilante, C. L.; Grosso, L.; Marsh, S.; Langaee, T.; Farnett, L. E.; Voora, D.; Veenstra, D. L.; Glynn, R. J.; Barrett, A.; McLeod, H. L.
- Abstract
Initiation of warfarin therapy using trial-and-error dosing is problematic. Our goal was to develop and validate a pharmacogenetic algorithm. In the derivation cohort of 1,015 participants, the independent predictors of therapeutic dose were: VKORC1 polymorphism −1639/3673 G>A (−28% per allele), body surface area (BSA) (+11% per 0.25 m2), CYP2C9*3 (−33% per allele), CYP2C9*2 (−19% per allele), age (−7% per decade), target international normalized ratio (INR) (+11% per 0.5 unit increase), amiodarone use (−22%), smoker status (+10%), race (−9%), and current thrombosis (+7%). This pharmacogenetic equation explained 53–54% of the variability in the warfarin dose in the derivation and validation (N= 292) cohorts. For comparison, a clinical equation explained only 17–22% of the dose variability (P < 0.001). In the validation cohort, we prospectively used the pharmacogenetic-dosing algorithm in patients initiating warfarin therapy, two of whom had a major hemorrhage. To facilitate use of these pharmacogenetic and clinical algorithms, we developed a nonprofit website, http://www.WarfarinDosing.org.Clinical Pharmacology & Therapeutics (2008); 84, 3, 326–331 doi:10.1038/clpt.2008.10
- Subjects
DRUG dosage; WARFARIN; PHARMACOGENOMICS; GENETIC polymorphisms; BIOCHEMICAL genetics; MEDICAL genetics
- Publication
Clinical Pharmacology & Therapeutics, 2008, Vol 84, Issue 3, p326
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2008.10