The influence of genetic polymorphisms and interacting drugs on initial response to warfarin in Chinese patients with heart valve replacement
| Autor: | Dan Xu, Hong-hong Tan, Hai-Yan Lao, Shi-Long Zhong, Min Yang, Xi-Yong Yu, Qiu-Xiong Lin, Shu-Guang Lin, Yuan Liu |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype medicine.drug_class Pharmacology Biology Polymorphism Single Nucleotide Gastroenterology Cardiac Valve Annuloplasty Mixed Function Oxygenases Asian People Cytochrome P-450 Enzyme System Internal medicine medicine Humans Drug Interactions Pharmacology (medical) International Normalized Ratio CYP2C9 Cytochrome P-450 CYP2C9 Retrospective Studies Body surface area Polymorphism Genetic Dose-Response Relationship Drug Anticoagulant Hazard ratio Warfarin Anticoagulants General Medicine Middle Aged Heart Valves Vitamin-K-epoxide reductase (warfarin-sensitive) Haplotypes Drug Therapy Combination Female Aryl Hydrocarbon Hydroxylases VKORC1 Pharmacogenetics medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 67:581-590 |
| ISSN: | 1432-1041 0031-6970 |
| DOI: | 10.1007/s00228-011-0995-6 |
| Popis: | Compared with genetic factors, drug interactions were largely unexplored in warfarin pharmacogenetic studies. This study sought to systematically investigate the effects of genetic polymorphisms of VKORC1, STX4A, CYP2C9, CYP3A4, and GGCX and interacting drugs on the initial responses to warfarin in Chinese patients with heart valve replacement (HVR).A retrospective study was conducted in 809 patients starting warfarin therapy after HVR. The relationships between 12 polymorphisms plus 47 drugs and primary outcomes of the time to the first international normalized ratio (INR) ≥ 1.8 and the time to the first INR3.5 and the secondary outcomes of the proportion of time INR1.8, the proportion of time INR3.5, and the daily warfarin dose in the first 28 days after the initiation of warfarin treatment were analyzed.Genetic polymorphisms and interacting drugs could significantly affect the primary and secondary outcomes. The time to the first INR ≥ 1.8 was significantly influenced by the body surface area (BSA), VKORC1 g.3588GA allele, and CYP2C9*3 allele, with hazard ratio (HR; 95% confidence interval [CI]) of 0.34 (0.17-0.66), 2.71 (2.2-3.35) and 1.43 (1.07-1.93) respectively. The time to the first INR3.5 was affected not only by BSA, VKORC1 g.3588GA allele, and CYP2C9*3 allele with HR (95%CI) of 0.26 (0.07-0.99), 2.76 (1.61-4.72), and 3.09 (2.02-4.74) respectively, but also by age and interacting drugs, including fluconazole, amiodarone, and simvastatin with HR (95%CI) of 1.02 (1.01-1.04), 2.66 (1.16-6.08), 1.78 (1.17-2.73), and 5.33 (1.67-16.96) respectively.Not only VKORC1 and CYP2C9 genotypes, but also interacting drugs, had a significant impact on the variability of the initial response to warfarin. |
| Databáze: | OpenAIRE |
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