title: Implications of Inter-Individual Differences in Clopidogrel Metabolism, with Focus on Pharmacogenetics.
abstract: Increasing evidence for the role of pharmacogenetics in treatment resistance to the antiplatelet agent clopidogrel has been gained during the last years. Apart fromCYP2C19genetic polymorphisms, nongenetic factors, particularly drug-drug interactions, age and other clinical characteristics influence the interindividual variability in clopidogrel response to varying degrees. The present article reviews the so far accumulated evidence on the role of pharmacogenetic traits influencing CYP-activity as determinants of the antiplatelet response to clopidogrel, and its clinical implications. The genetic variation in CYP2C19 activity seems to influence short- and long-term antithrombotic effects of clopidogrel to a substantial extent. Prediction models for clopidogrel non-responsiveness that includeCYP2C19genotyping together with relevant non-genetic risk factors are needed to be verified for their potential benefit in individualization of antithrombotic therapy.
authors.affiliation: Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden. marja-liisa.dahl@karolinska.se.|Department of Clinical Pharmacology, Karolinska University Hospital, Huddinge C1:68, SE-141 86, Stockholm, Sweden. marja-liisa.dahl@karolinska.se.
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Dahl
authors.affiliation: Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: Arzu
authors.initials: A
authors.lastname: Gunes
keywords: CYP2C19; antiplatelet response; clopidogrel; pharmacogenetics