title: The influence of omeprazole on platelet inhibition of clopidogrel in various CYP2C19 mutant alleles.
abstract: Currently, concerns of clopidogrel and proton pump inhibitors (especially omeprazole) interaction are raised, because they are both metabolized by CYP2C19. What is more, omeprazole can also inhibit the activity of CYP2C19. The study was to compare the influence of omeprazole on platelet inhibition of clopidogrel in various CYP2C19 mutant alleles. One hundred forty-two consecutive patients undergoing elective coronary stenting received aspirin and clopidogrel, and were randomized to omeprazole or the placebo. Enrolled patients were analyzed for adenosine diphosphate-induced platelet aggregation (ADP-Ag), and CYP2C19*2 and CYP2C19*3 were identified by polymerase chain reaction-restriction fragment length polymorphism. Of the patients included, 47 (33.1%) belonged to homozygous extensive metabolizers (homEMs) (CYP2C19*1/*1), 70 (49.3%) belonged to heterozygous extensive metabolizers (hetEMs) (*1/*2 or *1/*3), and 25 (17.6%) belonged to poor metabolizers (PMs) (*2/*3 or *2/*2). ADP-Ag had a significant difference among the three genotypic groups (p<0.01). Moreover, the present study revealed that the degree of the interaction between clopidogrel and omeprazole was not homogeneous within the various genotypes of CYP2C19. The difference of ADP-Ag between the patients with and without omeprazole was significantly largest in homEMs (45.7%±14.2% vs. 35.5%±16.0%, p<0.05). However, any significant difference of ADP-Ag between the patients with and without omeprazole was not observed in other two genotypic groups (hetEMs and PMs, p>0.05). In conclusion, concomitant therapy with omeprazole appears to reduce the antiplatelet effect of clopidogrel most significantly in homEMs of CYP2C19.
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Da-Sheng
authors.initials: DS
authors.lastname: Dang
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Guo-Bing
authors.initials: GB
authors.lastname: Shi
authors.forename: Qing-Chun
authors.initials: QC
authors.lastname: Zhao
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000494:pharmacology* / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D013988:Ticlopidine; D001241:Aspirin