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Article: Variability in response to clopidogrel: How important are pharmacogenetics and drug interactions?

TitleVariability in response to clopidogrel: How important are pharmacogenetics and drug interactions?
Authors
KeywordsClopidogrel
P 2Y 12 inhibitors
Pharmacogenetics
Proton pump inhibitor
Issue Date2011
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJCP
Citation
British Journal Of Clinical Pharmacology, 2011, v. 72 n. 4, p. 697-706 How to Cite?
AbstractClopidogrel is a pro-drug which is converted to an active metabolite that selectively blocks ADP-dependent platelet activation and aggregation. The main enzyme responsible for activating clopidogrel is the cytochrome P450 (CYP) isoenzyme CYP2C19, which is polymorphic. There is a growing body of literature showing that carriers of variant CYP2C19 alleles have impaired ability to metabolize clopidogrel (i.e. poor metabolizers), which is associated with decreased inhibition of platelet aggregation and increased cardiovascular risk. Some proton pump inhibitors are also metabolized by the CYP2C19 enzyme and often given together with clopidogrel to reduce gastrointestinal side effects. In particular, omeprazole has been shown to inhibit the CYP-mediated metabolism of clopidogrel, and some studies have shown that the combination was associated with a higher incidence of cardiovascular adverse reactions than clopidogrel given alone. However, a recent randomized controlled trial demonstrated no significant difference in adverse cardiovascular events for patients on the combination of clopidogrel and omeprazole compared with clopidogrel alone. This current review aims to summarize the role of pharmacogenetics and drug interactions in determining variability in response to clopidogrel. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
Persistent Identifierhttp://hdl.handle.net/10722/139501
ISSN
2015 Impact Factor: 3.83
2015 SCImago Journal Rankings: 1.486
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMa, TKWen_HK
dc.contributor.authorLam, YYen_HK
dc.contributor.authorTan, VPen_HK
dc.contributor.authorYan, BPen_HK
dc.date.accessioned2011-09-23T05:50:43Z-
dc.date.available2011-09-23T05:50:43Z-
dc.date.issued2011en_HK
dc.identifier.citationBritish Journal Of Clinical Pharmacology, 2011, v. 72 n. 4, p. 697-706en_HK
dc.identifier.issn0306-5251en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139501-
dc.description.abstractClopidogrel is a pro-drug which is converted to an active metabolite that selectively blocks ADP-dependent platelet activation and aggregation. The main enzyme responsible for activating clopidogrel is the cytochrome P450 (CYP) isoenzyme CYP2C19, which is polymorphic. There is a growing body of literature showing that carriers of variant CYP2C19 alleles have impaired ability to metabolize clopidogrel (i.e. poor metabolizers), which is associated with decreased inhibition of platelet aggregation and increased cardiovascular risk. Some proton pump inhibitors are also metabolized by the CYP2C19 enzyme and often given together with clopidogrel to reduce gastrointestinal side effects. In particular, omeprazole has been shown to inhibit the CYP-mediated metabolism of clopidogrel, and some studies have shown that the combination was associated with a higher incidence of cardiovascular adverse reactions than clopidogrel given alone. However, a recent randomized controlled trial demonstrated no significant difference in adverse cardiovascular events for patients on the combination of clopidogrel and omeprazole compared with clopidogrel alone. This current review aims to summarize the role of pharmacogenetics and drug interactions in determining variability in response to clopidogrel. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.en_HK
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJCPen_HK
dc.relation.ispartofBritish Journal of Clinical Pharmacologyen_HK
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subjectClopidogrelen_HK
dc.subjectP 2Y 12 inhibitorsen_HK
dc.subjectPharmacogeneticsen_HK
dc.subjectProton pump inhibitoren_HK
dc.subject.meshCytochrome P-450 Enzyme System - genetics-
dc.subject.meshPlatelet Aggregation - drug effects - genetics-
dc.subject.meshPlatelet Aggregation Inhibitors - pharmacology-
dc.subject.meshPolymorphism, Genetic - drug effects-
dc.subject.meshTiclopidine - analogs and derivatives - pharmacology-
dc.titleVariability in response to clopidogrel: How important are pharmacogenetics and drug interactions?en_HK
dc.typeArticleen_HK
dc.identifier.emailTan, VP:vpytan@hku.hken_HK
dc.identifier.authorityTan, VP=rp01458en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1365-2125.2011.03949.xen_HK
dc.identifier.pmid21352268en_HK
dc.identifier.pmcidPMC3195744-
dc.identifier.scopuseid_2-s2.0-80052642128en_HK
dc.identifier.hkuros196570en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80052642128&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume72en_HK
dc.identifier.issue4en_HK
dc.identifier.spage697en_HK
dc.identifier.epage706en_HK
dc.identifier.isiWOS:000294905500015-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridMa, TKW=31967717200en_HK
dc.identifier.scopusauthoridLam, YY=13003018600en_HK
dc.identifier.scopusauthoridTan, VP=24449627600en_HK
dc.identifier.scopusauthoridYan, BP=7201858670en_HK

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