Warfarin dosing algorithm using clinical, demographic and pharmacogenetic data from Chinese patients
| Autor: | Mary M.Y. Waye, Raymond S.M. Wong, Gregory Cheng, Joyce H. S. You, Yawei Mu, Cadmon K.P. Lim, Kai Chow Choi |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Vitamin K Genotype Mixed Function Oxygenases Asian People Internal medicine Vitamin K Epoxide Reductases medicine Humans CYP2C9 Aged Cytochrome P-450 CYP2C9 business.industry Maintenance dose Medical record Body Weight Warfarin Age Factors Anticoagulants Hematology Vitamins Stepwise regression Middle Aged Surgery Cross-Sectional Studies Cohort Hong Kong Female VKORC1 Aryl Hydrocarbon Hydroxylases Cardiology and Cardiovascular Medicine business Pharmacogenetics medicine.drug Follow-Up Studies |
| Zdroj: | Journal of thrombosis and thrombolysis. 31(1) |
| ISSN: | 1573-742X |
| Popis: | CYP2C9 and VKORC1 genotypes could be used to predict warfarin requirement. The objective was to develop and validate a warfarin dosing algorithm using genetic, clinical and demographic data of Chinese patients from an anticoagulation clinic in Hong Kong. Blood samples were collected from 100 patients on stable maintenance dose of warfarin, recruited from an anticoagulation clinic, for genotyping CYP2C9 and VKORC1. Clinical and demographic data were obtained by face-to-face interview and medical chart review. Data of 80 patients (study cohort) were randomly selected for deriving a dosing algorithm. Comparison between predicted dose and actual stable doses was conducted in a validation cohort (n = 20). Sixty-nine (69%) of all 100 patients were homozygous for VKORC1 1173-TT, 25 (25%) were VKORC1 1173-CT heterozygotes and six (6%) were homozygous for VKORC1 1173-CC. 6 (6%) patients were CYP2C9 1*/3* and 94 (94%) were CYP2C9 1*/1*. CYP2C9 and VKORC1 genotype, age, weight and vitamin K intake were identified by stepwise regression modelling to produce the best model for estimating warfarin dose (R (2) = 68%, P0.001). In the validation cohort (n = 20), actual stable dose was significantly associated with predicted dose (R = 0.6, P = 0.005). Five of 11 (45.6%) and 5/9 (55.6%) patients whose mean warfarin requirements were ≤ 3 mg/day and3 mg/day, respectively, were within20% of actual doses. In conclusion, a genotype-guided dosing algorithm for warfarin therapy was developed for Chinese patients to explain 68% of dosage variation. The predicted doses differed from the actual doses by no more than 20% in 50% of patients. |
| Databáze: | OpenAIRE |
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