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Title: P-Glycoprotein Polymorphism C3435T Is Associated with Dose-Adjusted Clopidogrel and 2-Oxo-Clopidogrel Concentration
Authors: Stokanovic, Dragana
Nikolic V.
Konstantinovic, Sandra
Zvezdanović, Jelena
Lilic J.
Apostolovic, Svetlana
Pavlović, Milan
Zivkovic V.
Jevtovic Stoimenov, Tatjana
Jankovic, Slobodan
Issue Date: 2016
Abstract: © 2015 S. Karger AG, Basel. Background/Aims: One of the most common polymorphisms of ABCB1 gene, a synonymous mutation C3435T (rs1045642), is associated with increased in vivo activity. The main goal of this study was to determine the association of C3435T polymorphism with clopidogrel and 2-oxo-clopidogrel concentrations in plasma. Methods: The patients were recruited upon acute myocardial infarction diagnosis. They were all tested for ABCB1 C3435T polymorphism. In plasma, drawn 1 h after the drug administration, concentrations of clopidogrel and 2-oxo-clopidogrel were measured using UHPLC-DAD-MS analysis. Results: Due to differences in the maintenance doses, we have calculated the dose-adjusted concentrations of clopidogrel (0.2 ng/ml/mg (0.1-0.4)) and 2-oxo-clopidogrel (2.1 ng/ml/mg (0.5-4.6)). Patients carrying at least one C allele achieved significantly higher serum concentration of clopidogrel (p < 0.001), as well as dose-adjusted clopidogrel (p < 0.001) and 2-oxo-clopidogrel concentrations (p < 0.05). Conclusion: The ABCB1 3435CC genotype is associated with increased clopidogrel and 2-oxo-clopidogrel dose-adjusted concentrations. Therefore, the ABCB1 C3435T genotyping should be one of the parameters taken into account when deciding about the dosing regimen of clopidogrel.
Type: article
DOI: 10.1159/000442712
ISSN: 0031-7012
SCOPUS: 2-s2.0-84953707751
Appears in Collections:Faculty of Medical Sciences, Kragujevac

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