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

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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

Titel: Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated Metabolism of Montelukast in Humans.
Författare: Itkonen, Matti K.; Tornio, Aleksi; Filppula, Anne M.; Neuvonen, Mikko; Neuvonen, Pertti J.; Niemi, Mikko; Backman, Janne T.
Upphovmannens organisation: Medicum
Department of Clinical Pharmacology
University of Helsinki
Janne Backman / Principal Investigator
HUSLAB
Datum: 2018-09
Språk: eng
Sidantal: 10
Tillhör serie: Clinical Pharmacology and Therapeutics
ISSN: 0009-9236
DOI: https://doi.org/10.1002/cpt.947
Permanenta länken (URI): http://hdl.handle.net/10138/243764
Abstrakt: 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.
Subject: ACUTE CORONARY SYNDROMES
CYP2C8 SUBSTRATE PIOGLITAZONE
DRUG-DRUG INTERACTIONS
GEMFIBROZIL
LEUKOTRIENE-RECEPTOR ANTAGONIST
MARKEDLY INCREASES
PHARMACOKINETICS
PLASMA-CONCENTRATIONS
3121 General medicine, internal medicine and other clinical medicine
Referentgranskad: Ja
Licens: unspecified
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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