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The Influence of Omeprazole on Platelet Inhibition of Clopidogrel in Various CYP2C19 Mutant Alleles.
MedLine Citation:
PMID:  23046071     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Qian Liu; Da-Sheng Dang; Yu-Feng Chen; Ming Yan; Guo-Bing Shi; Qing-Chun Zhao
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-9
Journal Detail:
Title:  Genetic testing and molecular biomarkers     Volume:  -     ISSN:  1945-0257     ISO Abbreviation:  Genet Test Mol Biomarkers     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101494210     Medline TA:  Genet Test Mol Biomarkers     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Department of Pharmacy, General Hospital of Shenyang Military Area Command , Shenyang, China .
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