Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated Metabolism of Montelukast in Humans.

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dc.contributor.author Itkonen, Matti K.
dc.contributor.author Tornio, Aleksi
dc.contributor.author Filppula, Anne M.
dc.contributor.author Neuvonen, Mikko
dc.contributor.author Neuvonen, Pertti J.
dc.contributor.author Niemi, Mikko
dc.contributor.author Backman, Janne T.
dc.date.accessioned 2018-09-20T07:12:01Z
dc.date.available 2018-09-20T07:12:01Z
dc.date.issued 2018-09
dc.identifier.citation Itkonen , M K , Tornio , A , Filppula , A M , Neuvonen , M , Neuvonen , P J , Niemi , M & Backman , J T 2018 , ' Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated Metabolism of Montelukast in Humans. ' , Clinical Pharmacology and Therapeutics , vol. 104 , no. 3 , pp. 495-504 . https://doi.org/10.1002/cpt.947
dc.identifier.other PURE: 97818068
dc.identifier.other PURE UUID: 4a607f72-88ee-43d8-b829-bdf07efc2d2d
dc.identifier.other Scopus: 85038968903
dc.identifier.other WOS: 000442734000013
dc.identifier.other ORCID: /0000-0002-9577-2788/work/48610093
dc.identifier.other ORCID: /0000-0003-3631-9411/work/48611516
dc.identifier.other ORCID: /0000-0001-5713-5692/work/48611836
dc.identifier.uri http://hdl.handle.net/10138/243764
dc.description.abstract The oxidation of montelukast is mainly mediated by cytochrome P450 (CYP) 2C8, but other mechanisms may contribute to its disposition. In healthy volunteers, we investigated the effects of two widely used P2Y(12) inhibitors on montelukast pharmacokinetics. Clopidogrel (300mg on day 1 and 75mg on day 2) increased the area under the plasma concentration-time curve (AUC) of montelukast 2.0-fold (90% confidence interval (CI) 1.72-2.28, P <0.001) and decreased the M6:montelukast AUC(0-7h) ratio to 45% of control (90% CI 40-50%, P <0.001). Prasugrel (60mg on day 1 and 10mg on day 2) had no clinically meaningful effect on montelukast pharmacokinetics. Our results imply that clopidogrel is at least a moderate inhibitor of CYP2C8, but prasugrel is not a clinically relevant CYP2C8 inhibitor. The different interaction potentials of clopidogrel and prasugrel are important to consider when antiplatelet therapy is planned for patients at risk for polypharmacy with CYP2C8 substrates. en
dc.format.extent 10
dc.language.iso eng
dc.relation.ispartof Clinical Pharmacology and Therapeutics
dc.rights unspecified
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject ACUTE CORONARY SYNDROMES
dc.subject CYP2C8 SUBSTRATE PIOGLITAZONE
dc.subject DRUG-DRUG INTERACTIONS
dc.subject GEMFIBROZIL
dc.subject LEUKOTRIENE-RECEPTOR ANTAGONIST
dc.subject MARKEDLY INCREASES
dc.subject PHARMACOKINETICS
dc.subject PLASMA-CONCENTRATIONS
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated Metabolism of Montelukast in Humans. en
dc.type Article
dc.contributor.organization Medicum
dc.contributor.organization Department of Clinical Pharmacology
dc.contributor.organization University of Helsinki
dc.contributor.organization Janne Backman / Principal Investigator
dc.contributor.organization HUSLAB
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1002/cpt.947
dc.relation.issn 0009-9236
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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