Impact of CYP2C9 polymorphisms on the vulnerability to pharmacokinetic drug-drug interactions during acenocoumarol treatment

Article Article scientifique Article Impact of CYP2C9 polymorphisms on the vulnerability to pharmacokinetic drug-drug interactions during acenocoumarol treatment eng 2013 author Gschwind Liliane 640977 author Rollason Victoria 40955 Victoria Rollason Gumprecht author Boehlen Françoise 33004 author Rebsamen Michela 83022 author Combescure Christophe 0000-0003-2631-4780 670542 author Grunenwald Michèle Fernande 88948 author Matthey Alain 558446 author Bonnabry Pascal 21883 author Dayer Pierre 25460 author Desmeules Jules Alexandre 73542 745-753 10.2217/pgs.13.55 23651023 1462-2416 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. Original submitted 29 October 2012; Revision submitted 5 March 2013. Dewey 615 Dewey 616 Dewey 617 31 Section des sciences pharmaceutiques 17 56 Département de médecine 221 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 false 88 Epidémiologie clinique 115 302 Groupe Desmeules Jules (pharmacologie/toxicologie) 567 Pharmacogenomics 14 7 38d23d44-751d-4360-8696-891a37aeae8e Article (Published version) Restricted Pages_de_PDthesis_rollason_16.12.2019_archiveouverte.pdf 532961 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences

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Impact of CYP2C9 polymorphisms on the vulnerability to pharmacokinetic drug-drug interactions during acenocoumarol treatment	Pharmacogenomics			2013	638	0

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Grunenwald, Michèle Fernande