Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated Metabolism of Montelukast in Humans.
Clin Pharmacol Ther
; 104(3): 495-504, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-29171020
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 P2Y12 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 M6montelukast AUC0-7h 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
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Inibidores da Agregação Plaquetária
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Antagonistas de Leucotrienos
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Citocromo P-450 CYP2C8
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Inibidores do Citocromo P-450 CYP2C8
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Cloridrato de Prasugrel
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Clopidogrel
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Acetatos
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Risk_factors_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article