Gemfibrozil markedly increases the plasma concentrations of montelukast: a previously unrecognized role for CYP2C8 in the metabolism of montelukast.
作者： T Karonen , A Filppula , J Laitila , M Niemi , P J Neuvonen
DOI: 10.1038/CLPT.2010.73
关键词: Crossover study 、 CYP2C8 、 Endocrinology 、 Glucuronide 、 Gemfibrozil 、 Placebo 、 Microsome 、 Internal medicine 、 Chemistry 、 Montelukast 、 Pharmacokinetics 、 Pharmacology
摘要: According to available information, montelukast is metabolized by cytochrome P450 (CYP) 3A4 and 2C9. In order study the significance of CYP2C8 in pharmacokinetics montelukast, 10 healthy subjects were administered gemfibrozil 600 mg or placebo twice daily for 3 days, on day 3, a randomized, crossover study. Gemfibrozil increased mean area under plasma concentration-time curve (AUC)(0-infinity), peak concentration (C(max)), elimination half-life (t(1/2)) 4.5-fold, 1.5-fold, 3.0-fold, respectively (P 90% < 0.001). human liver microsomes, 1-O-beta glucuronide inhibited formation M6 (but not M5) from 35-fold more potently than did (half-maximal inhibitory (IC(50)) 3.0 107 micromol/l, respectively). conclusion, markedly increases concentrations indicating that crucial montelukast.
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