Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance dose: a prospective study in Chinese patients
| Autor: | Xian-Qun Wang, Yan-Kai Jia, Zhi-Hui Huang, Liang Li, Dao-kang Xiang, Yong He, Hai-Sheng Chen, Xiao-Jia Hu, Hao-Fei Wang, Ling Huang, Ding-Li Xu, Xiang-Min Xu, Bao-Lin Chen, Shengwen Huang, Kai-Ming Chen, Qiang Li, Xiao-Ming Zou, Li-Qin Ma |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty China Genotype Pharmacology law.invention Mixed Function Oxygenases Randomized controlled trial Asian People law Internal medicine Vitamin K Epoxide Reductases Genetics medicine Humans Dosing General Pharmacology Toxicology and Pharmaceutics Prospective cohort study Molecular Biology Genetics (clinical) Aged Cytochrome P-450 CYP2C9 Maintenance dose business.industry Warfarin Anticoagulants Middle Aged Pharmacogenomics Molecular Medicine Regression Analysis Female VKORC1 Aryl Hydrocarbon Hydroxylases business Pharmacogenetics Algorithms medicine.drug |
| Zdroj: | Pharmacogenetics and genomics. 19(3) |
| ISSN: | 1744-6872 |
| Popis: | To develop a warfarin-dosing algorithm that could be combined with pharmacogenomic and demographic factors, and to evaluate its effectiveness in a randomized prospective controlled clinical trial.A pharmacogenetics-based dosing model was derived using retrospective data from 266 Chinese patients and multiple linear regression analysis. To prospectively validate this model, 156 patients with an operation of heart valve replacement were enrolled and randomly assigned to the group of pharmacogenetics-guided or traditional dosing for warfarin therapy. All patients were followed up for 50 days after initiation of warfarin therapy. The log-rank test was compared with the time-to-event (Kaplan-Meier) curves. Cox proportional hazards-regression model was used to assess the hazard ratio of the time to reach stable dose.The linear regression model derived from the pharmacogenomic model correlated with 54.1% of warfarin dosing variance. The final multiple linear regression model included age, body surface area, VKORC1, and CYP2C9 genotype. The study showed that the hazard ratio for the time to reach stable dose was 1.932 for the traditional dosing group versus the model-based group and a close and highly significant relationship was observed to exist between the predicted and the actual warfarin dose (R=0.454).A pharmacogenetics-based dosing algorithm has been developed for improvement in the time to reach the stable dosing of warfarin. This model may be useful in helping the clinicians to prescribe warfarin with greater safety and efficiency. |
| Databáze: | OpenAIRE |
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