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Pharmacogenomics ; 14(7): 745-53, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23651023

RESUMEN

AIM: The objective of this study was to investigate the impact of CYP2C9 polymorphisms and drug-drug interactions on the risk of overanticoagulation in patients treated with acenocoumarol, a vitamin K antagonist. MATERIALS & METHODS: A prospective observational study was performed on patients starting acenocoumarol (n = 115). CYP2C9 genotypes were assessed. Data on International Normalized Ratio, comedications and doses of acenocoumarol were collected during the first 35 days of therapy. Overanticoagulation was defined as the occurrence of at least one International Normalized Ratio ≥4. RESULTS: The presence of a CYP2C9 inhibitor or a CYP2C9 polymorphisms statistically increased the risk of overanticoagulation (hazard ratio [HR]: 2.8, p < 0.001 and HR: 1.7, p = 0.04, respectively). The presence of CYP2C9 polymorphisms almost tripled the risk of overanticoagulation (HR: 2.91, p = 0.01) in the presence of a clinically significant drug-drug interaction. CONCLUSION: These findings support the fact that CYP2C9 genotyping could be useful to identify patients requiring closer monitoring, especially when a drug-drug interaction is expected.


Asunto(s)
Acenocumarol/farmacocinética , Acenocumarol/uso terapéutico , Anticoagulantes/farmacocinética , Anticoagulantes/uso terapéutico , Hidrocarburo de Aril Hidroxilasas/genética , Hidrocarburo de Aril Hidroxilasas/metabolismo , Coagulación Sanguínea/efectos de los fármacos , Trastornos de la Coagulación Sanguínea/inducido químicamente , Trastornos de la Coagulación Sanguínea/enzimología , Trastornos de la Coagulación Sanguínea/genética , Citocromo P-450 CYP2C9 , Interacciones Farmacológicas , Femenino , Genotipo , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Estudios Prospectivos
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