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

Overview

Journal Clin Pharmacol Ther

Publisher Wiley

Specialty Pharmacology

Date 2017 Nov 25

PMID 29171020

Citations 6

Authors

Matti K Itkonen

Aleksi Tornio

Anne M Filppula

Mikko Neuvonen

Pertti J Neuvonen

Mikko Niemi

Janne T Backman

Affiliations

Soon will be listed here.

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 inhibitors on montelukast pharmacokinetics. Clopidogrel (300 mg on day 1 and 75 mg 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 ratio to 45% of control (90% CI 40-50%, P < 0.001). Prasugrel (60 mg on day 1 and 10 mg 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.

Citing Articles

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