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Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8‐Mediated Metabolism of Montelukast in Humans
Author(s) -
Itkonen Matti K.,
Tornio Aleksi,
Filppula Anne M.,
Neuvonen Mikko,
Neuvonen Pertti J.,
Niemi Mikko,
Backman Janne T.
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.947
Subject(s) - prasugrel , montelukast , clopidogrel , cyp2c8 , pharmacokinetics , pharmacology , cyp2c19 , medicine , ticlopidine , cyp3a4 , cytochrome p450 , metabolism , aspirin , asthma
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 (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 0‐7h 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.