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Clopidogrel but Not...
Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated Metabolism of Montelukast in Humans
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- Itkonen, Matti K. (author)
- Univ Helsinki, Dept Clin Pharmacol, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland
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- Tornio, Aleksi (author)
- Univ Helsinki, Dept Clin Pharmacol, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland
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- Filppula, Anne M. (author)
- Uppsala universitet,Institutionen för farmaci,Univ Helsinki, Dept Clin Pharmacol, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland
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- Neuvonen, Mikko (author)
- Univ Helsinki, Dept Clin Pharmacol, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland
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- Neuvonen, Pertti J. (author)
- Univ Helsinki, Dept Clin Pharmacol, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland
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- Niemi, Mikko (author)
- Univ Helsinki, Dept Clin Pharmacol, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland
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- Backman, Janne T. (author)
- Univ Helsinki, Dept Clin Pharmacol, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland
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(creator_code:org_t)
- 2017-12-23
- 2018
- English.
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In: Clinical Pharmacology and Therapeutics. - : Wiley. - 0009-9236 .- 1532-6535. ; 104:3, s. 495-504
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Abstract
Subject headings
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- 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 headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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