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Article: Impact of genetic and acquired alteration in cytochrome P450 system on pharmacologic and clinical response to clopidogrel

TitleImpact of genetic and acquired alteration in cytochrome P450 system on pharmacologic and clinical response to clopidogrel
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2010
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/pharmthera
Citation
Pharmacology And Therapeutics, 2010, v. 125 n. 2, p. 249-259 How to Cite?
AbstractDual antiplatelet therapy with aspirin and clopidogrel has been shown to reduce subsequent cardiac events in patients with acute coronary syndrome or coronary artery stenting. Clopidogrel, a thienopyridine, is a prodrug that is transformed in vivo to an active metabolite by the cytochrome P450 (CYP) enzyme system. The genes encoding CYP enzymes are polymorphic. Recent data demonstrated patients carrying a genetic variant of CYP enzymes (e.g. CYP2C19) would have a higher rate of ischemic events than non-carriers due to an attenuation of the pharmacokinetic and pharmacodynamic responses to clopidogrel. Furthermore, concomitant gastrointestinal ulcer prophylaxis with a proton pump inhibitor (PPI) is commonly prescribed to patients because of the increased risk of bleeding with dual antiplatelet therapy. PPIs are extensively metabolized by the cytochrome P450 system and have been associated with decreased antiplatelet activity of clopidogrel. In this review, we will discuss the impact of CYP450 enzymes genetic variation and CYP450 pathway drug-drug interactions in pharmacological and clinical response to clopidogrel. © 2009 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/132480
ISSN
2015 Impact Factor: 11.0
2015 SCImago Journal Rankings: 4.090
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMa, TKWen_HK
dc.contributor.authorLam, YYen_HK
dc.contributor.authorTan, VPen_HK
dc.contributor.authorKiernan, TJen_HK
dc.contributor.authorYan, BPen_HK
dc.date.accessioned2011-03-28T09:25:13Z-
dc.date.available2011-03-28T09:25:13Z-
dc.date.issued2010en_HK
dc.identifier.citationPharmacology And Therapeutics, 2010, v. 125 n. 2, p. 249-259en_HK
dc.identifier.issn0163-7258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132480-
dc.description.abstractDual antiplatelet therapy with aspirin and clopidogrel has been shown to reduce subsequent cardiac events in patients with acute coronary syndrome or coronary artery stenting. Clopidogrel, a thienopyridine, is a prodrug that is transformed in vivo to an active metabolite by the cytochrome P450 (CYP) enzyme system. The genes encoding CYP enzymes are polymorphic. Recent data demonstrated patients carrying a genetic variant of CYP enzymes (e.g. CYP2C19) would have a higher rate of ischemic events than non-carriers due to an attenuation of the pharmacokinetic and pharmacodynamic responses to clopidogrel. Furthermore, concomitant gastrointestinal ulcer prophylaxis with a proton pump inhibitor (PPI) is commonly prescribed to patients because of the increased risk of bleeding with dual antiplatelet therapy. PPIs are extensively metabolized by the cytochrome P450 system and have been associated with decreased antiplatelet activity of clopidogrel. In this review, we will discuss the impact of CYP450 enzymes genetic variation and CYP450 pathway drug-drug interactions in pharmacological and clinical response to clopidogrel. © 2009 Elsevier Inc.en_HK
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/pharmtheraen_HK
dc.relation.ispartofPharmacology and Therapeuticsen_HK
dc.subjectChemicals And Cas Registry Numbersen_US
dc.subject.meshAspirin - pharmacokinetics - therapeutic useen_HK
dc.subject.meshCalcium Channel Blockers - pharmacology - therapeutic useen_HK
dc.subject.meshCytochrome P-450 Enzyme System - genetics - metabolismen_HK
dc.subject.meshDrug Interactionsen_HK
dc.subject.meshDrug Resistanceen_HK
dc.subject.meshHumansen_HK
dc.subject.meshHydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology - therapeutic useen_HK
dc.subject.meshPlatelet Aggregation Inhibitors - pharmacokinetics - therapeutic useen_HK
dc.subject.meshPolymorphism, Geneticen_HK
dc.subject.meshPolypharmacyen_HK
dc.subject.meshProton Pump Inhibitors - pharmacology - therapeutic useen_HK
dc.subject.meshTiclopidine - analogs & derivatives - pharmacokinetics - therapeutic useen_HK
dc.titleImpact of genetic and acquired alteration in cytochrome P450 system on pharmacologic and clinical response to clopidogrelen_HK
dc.typeArticleen_HK
dc.identifier.emailTan, VP:vpytan@hku.hken_HK
dc.identifier.authorityTan, VP=rp01458en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.pharmthera.2009.10.008en_HK
dc.identifier.pmid19919843-
dc.identifier.scopuseid_2-s2.0-77249155077en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77249155077&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume125en_HK
dc.identifier.issue2en_HK
dc.identifier.spage249en_HK
dc.identifier.epage259en_HK
dc.identifier.isiWOS:000275356600005-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMa, TKW=31967717200en_HK
dc.identifier.scopusauthoridLam, YY=13003018600en_HK
dc.identifier.scopusauthoridTan, VP=24449627600en_HK
dc.identifier.scopusauthoridKiernan, TJ=26324986700en_HK
dc.identifier.scopusauthoridYan, BP=7201858670en_HK
dc.identifier.citeulike6184202-

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