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CYP2C19 genetic polymorphism, rabeprazole and esomeprazole have no effect on the antiplatelet action of clopidogrel

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dc.contributor.author El-Halabi M.M.
dc.contributor.author Zgheib N.
dc.contributor.author Mansour N.M.
dc.contributor.author Malli A.
dc.contributor.author Ghaith O.A.
dc.contributor.author Mahfouz R.
dc.contributor.author Alam S.
dc.contributor.author Sharara A.I.
dc.contributor.editor
dc.date Jul-2013
dc.date.accessioned 2017-10-05T16:02:44Z
dc.date.available 2017-10-05T16:02:44Z
dc.date.issued 2013
dc.identifier 10.1097/FJC.0b013e31828ecf44
dc.identifier.isbn
dc.identifier.issn 01602446
dc.identifier.uri http://hdl.handle.net/10938/19603
dc.description.abstract The aim of this study is to investigate the effect of CYP2C19 polymorphism and cotherapy with rabeprazole or esomeprazole on the antiplatelet effect of clopidogrel. Patients receiving clopidogrel 75 mg ± rabeprazole or esomeprazole underwent genotyping for CYP2C19*2 and CYP2C19*3, and vasodilator-stimulated phosphoprotein testing to measure platelet reactivity index (PRI). Two hundred thirty-nine consecutive patients were enrolled as follows: 92 clopidogrel (C group), 94 clopidogrel + rabeprazole (CR), and 53 clopidogrel + esomeprazole (CE). Forty-five patients had loss of function (LOF) polymorphism (43 heterozygous; 2 homozygous mutant for CYP2C19*2). The mean PRI was 20.7percent ± 21.9percent in the C group, 19.1percent ± 20.9percent in the CR group, and 24.5percent ± 22.9percent in the CE group (P = NS). High on-treatment platelet reactivity (HPR), defined as PRI 50percent, was observed in 12 (13.0percent), 13 (13.8percent), and 10 (18.9percent) patients on C, CR, and CE, respectively (P = NS). HPR was similar in rapid metabolizers between groups. On multivariate logistic regression, neither CYP2C19 LOF alleles nor proton pump inhibitor cotherapy were associated with HPR. The use of proton pump inhibitors was indicated in 30.6percent of recipients. As a conclusion, CYP2C19*2 LOF allele and the use of esomeprazole or rabeprazole have no effect on the action of clopidogrel. Copyright © 2013 by Lippincott Williams and Wilkins.
dc.format.extent
dc.format.extent Pages: (41-49)
dc.language English
dc.publisher PHILADELPHIA
dc.relation.ispartof Publication Name: Journal of Cardiovascular Pharmacology; Publication Year: 2013; Volume: 62; no. 1; Pages: (41-49);
dc.relation.ispartofseries
dc.relation.uri
dc.source Scopus
dc.subject.other
dc.title CYP2C19 genetic polymorphism, rabeprazole and esomeprazole have no effect on the antiplatelet action of clopidogrel
dc.type Article
dc.contributor.affiliation El-Halabi, M.M., Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, PO Box 11-0236-16-B, Beirut, Lebanon
dc.contributor.affiliation Zgheib, N., Department of Pharmacology and Toxicology, American University of Beirut Medical Center, Beirut, Lebanon
dc.contributor.affiliation Mansour, N.M., Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, PO Box 11-0236-16-B, Beirut, Lebanon
dc.contributor.affiliation Malli, A., Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, PO Box 11-0236-16-B, Beirut, Lebanon
dc.contributor.affiliation Ghaith, O.A., Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, PO Box 11-0236-16-B, Beirut, Lebanon
dc.contributor.affiliation Mahfouz, R., Department of Pathology, Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon
dc.contributor.affiliation Alam, S., Division of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
dc.contributor.affiliation Sharara, A.I., Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, PO Box 11-0236-16-B, Beirut, Lebanon
dc.contributor.authorAddress Sharara, A.I.; Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, PO Box 11-0236-16-B, Beirut, Lebanon; email: as08@aub.edu.lb
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Pharmacology and Toxicology;
dc.contributor.authorDepartment Pharmacology and Toxicology
dc.contributor.authorDivision
dc.contributor.authorEmail as08@aub.edu.lb
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials El-Halabi, MM
dc.contributor.authorInitials Zgheib, N
dc.contributor.authorInitials Mansour, NM
dc.contributor.authorInitials Malli, A
dc.contributor.authorInitials Ghaith, OA
dc.contributor.authorInitials Mahfouz, R
dc.contributor.authorInitials Alam, S
dc.contributor.authorInitials Sharara, AI
dc.contributor.authorOrcidID
dc.contributor.authorReprintAddress Sharara, AI (reprint author), Amer Univ Beirut, Med Ctr, Div Gastroenterol, POB 11-0236-16-B, Beirut, Lebanon.
dc.contributor.authorResearcherID
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.description.citedCount 6
dc.description.citedTotWOSCount 5
dc.description.citedWOSCount 4
dc.format.extentCount 9
dc.identifier.articleNo
dc.identifier.coden JCPCD
dc.identifier.pubmedID 23474843
dc.identifier.scopusID 84880570065
dc.identifier.url
dc.publisher.address 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
dc.relation.ispartofConference
dc.relation.ispartofConferenceCode
dc.relation.ispartofConferenceDate
dc.relation.ispartofConferenceHosting
dc.relation.ispartofConferenceLoc
dc.relation.ispartofConferenceSponsor
dc.relation.ispartofConferenceTitle
dc.relation.ispartofFundingAgency
dc.relation.ispartOfISOAbbr J. Cardiovasc. Pharmacol.
dc.relation.ispartOfIssue 1
dc.relation.ispartOfPart
dc.relation.ispartofPubTitle Journal of Cardiovascular Pharmacology
dc.relation.ispartofPubTitleAbbr J. Cardiovasc. Pharmacol.
dc.relation.ispartOfSpecialIssue
dc.relation.ispartOfSuppl
dc.relation.ispartOfVolume 62
dc.source.ID WOS:000322113200006
dc.type.publication Journal
dc.subject.otherAuthKeyword CYP450
dc.subject.otherAuthKeyword drug interaction
dc.subject.otherAuthKeyword high on-treatment platelet reactivity
dc.subject.otherAuthKeyword metabolism
dc.subject.otherAuthKeyword pharmacodynamic
dc.subject.otherAuthKeyword platelet reactivity index
dc.subject.otherAuthKeyword proton pump inhibitors
dc.subject.otherChemCAS acetylsalicylic acid, 493-53-8, 50-78-2, 53663-74-4, 53664-49-6, 63781-77-1
dc.subject.otherChemCAS clopidogrel, 113665-84-2, 120202-66-6, 90055-48-4, 94188-84-8
dc.subject.otherChemCAS esomeprazole, 119141-88-7, 161796-84-5, 202742-32-3, 217087-09-7, 217087-10-0
dc.subject.otherChemCAS prostaglandin E1, 745-65-3
dc.subject.otherChemCAS rabeprazole, 117976-89-3, 117976-90-6
dc.subject.otherChemCAS Aryl Hydrocarbon Hydroxylases, 1.14.14.1
dc.subject.otherChemCAS CYP2C19 protein, human, 1.14.14.1
dc.subject.otherChemCAS Esomeprazole, N3PA6559FT
dc.subject.otherChemCAS Platelet Aggregation Inhibitors
dc.subject.otherChemCAS Proton Pump Inhibitors
dc.subject.otherChemCAS Rabeprazole, 32828355LL
dc.subject.otherChemCAS Ticlopidine, OM90ZUW7M1
dc.subject.otherChemCAS clopidogrel, A74586SNO7
dc.subject.otherIndex acetylsalicylic acid
dc.subject.otherIndex clopidogrel
dc.subject.otherIndex cytochrome P450 2C19
dc.subject.otherIndex esomeprazole
dc.subject.otherIndex prostaglandin E1
dc.subject.otherIndex rabeprazole
dc.subject.otherIndex vasodilator stimulated phosphoprotein
dc.subject.otherIndex adult
dc.subject.otherIndex aged
dc.subject.otherIndex allele
dc.subject.otherIndex anticoagulant therapy
dc.subject.otherIndex article
dc.subject.otherIndex controlled study
dc.subject.otherIndex drug effect
dc.subject.otherIndex drug metabolism
dc.subject.otherIndex dyspepsia
dc.subject.otherIndex female
dc.subject.otherIndex gastroesophageal reflux
dc.subject.otherIndex gastrointestinal hemorrhage
dc.subject.otherIndex genotype
dc.subject.otherIndex heterozygosity
dc.subject.otherIndex homozygosity
dc.subject.otherIndex human
dc.subject.otherIndex major clinical study
dc.subject.otherIndex male
dc.subject.otherIndex peptic ulcer
dc.subject.otherIndex platelet reactivity
dc.subject.otherIndex priority journal
dc.subject.otherIndex protein phosphorylation
dc.subject.otherIndex single nucleotide polymorphism
dc.subject.otherIndex treatment duration
dc.subject.otherIndex Aged
dc.subject.otherIndex Aryl Hydrocarbon Hydroxylases
dc.subject.otherIndex Blood Platelets
dc.subject.otherIndex Cohort Studies
dc.subject.otherIndex Esomeprazole
dc.subject.otherIndex Female
dc.subject.otherIndex Genotype
dc.subject.otherIndex Humans
dc.subject.otherIndex Logistic Models
dc.subject.otherIndex Male
dc.subject.otherIndex Platelet Aggregation
dc.subject.otherIndex Platelet Aggregation Inhibitors
dc.subject.otherIndex Polymorphism, Genetic
dc.subject.otherIndex Prospective Studies
dc.subject.otherIndex Proton Pump Inhibitors
dc.subject.otherIndex Rabeprazole
dc.subject.otherIndex Ticlopidine
dc.subject.otherKeywordPlus PROTON-PUMP INHIBITORS
dc.subject.otherKeywordPlus TREATMENT PLATELET REACTIVITY
dc.subject.otherKeywordPlus EXPERT CONSENSUS DOCUMENTS
dc.subject.otherKeywordPlus FOUNDATION TASK-FORCE
dc.subject.otherKeywordPlus PERCUTANEOUS CORONARY INTERVENTION
dc.subject.otherKeywordPlus OF-FUNCTION POLYMORPHISM
dc.subject.otherKeywordPlus CONCOMITANT USE
dc.subject.otherKeywordPlus CARDIOVASCULAR EVENTS
dc.subject.otherKeywordPlus ATHEROTHROMBOTIC EVENTS
dc.subject.otherKeywordPlus GASTROINTESTINAL RISKS
dc.subject.otherWOS Cardiac and Cardiovascular Systems
dc.subject.otherWOS Pharmacology and Pharmacy


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