title: Differential impacts of CYP2C19 gene polymorphisms on the antiplatelet effects of clopidogrel and ticlopidine.
abstract: We examined the influence of CYP2C19 polymorphisms on the antiplatelet effects of clopidogrel and ticlopidine. The platelet aggregation induced by 20 µmol/l adenosine diphosphate (ADP) and CYP2C19 single-nucleotide polymorphisms (*2 and *3) was determined in patients with coronary artery disease (CAD) who were taking aspirin alone (n = 21), aspirin plus clopidogrel (n = 97), or aspirin plus ticlopidine (n = 47). The degree of platelet aggregation in the clopidogrel group, although not in the ticlopidine group, depended on the CYP2C19 polymorphism, and the maximal platelet aggregation in poor metabolizers (PMs) taking clopidogrel was equivalent to that in the group taking aspirin alone. After being switched from clopidogrel to ticlopidine, all seven of the PMs showed markedly lower platelet aggregation. These results suggest that CYP2C19 polymorphisms have a profound impact on the antiplatelet effect of clopidogrel but not on that of ticlopidine. Ticlopidine may be an effective therapeutic option for CYP2C19 PMs.
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Maeda
authors.forename: H
authors.initials: H
authors.lastname: Ando
authors.forename: T
authors.initials: T
authors.lastname: Asai
authors.forename: H
authors.initials: H
authors.lastname: Ishiguro
authors.forename: N
authors.initials: N
authors.lastname: Umemoto
authors.forename: M
authors.initials: M
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Morishima
authors.forename: A
authors.initials: A
authors.lastname: Sumida
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Hosohata
authors.forename: K
authors.initials: K
authors.lastname: Ushijima
authors.forename: A
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine