title: P-Glycoprotein Polymorphism C3435T Is Associated with Dose-Adjusted Clopidogrel and 2-Oxo-Clopidogrel Concentration.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Nis, Faculty of Medicine, Leskovac, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Stokanovic
authors.forename: Valentina N
authors.initials: VN
authors.lastname: Nikolic
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Konstantinovic
authors.forename: Jelena B
authors.initials: JB
authors.lastname: Zvezdanovic
authors.forename: Jelena
authors.initials: J
authors.lastname: Lilic
authors.forename: Svetlana R
authors.initials: SR
authors.lastname: Apostolovic
authors.forename: Milan
authors.initials: M
authors.lastname: Pavlovic
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Zivkovic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Jevtovic-Stoimenov
authors.forename: Slobodan M
authors.initials: SM
authors.lastname: Jankovic
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077144:Clopidogrel; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010975:Platelet Aggregation Inhibitors; C540904:2-oxo-clopidogrel; D000077144:Clopidogrel; D013988:Ticlopidine