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Effect of multiple doses of montelukast on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in humans
Author(s) -
Kim KyoungAh,
Park PilWhan,
Kim Kyong Rae,
Park JiYoung
Publication year - 2007
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2006.02764.x
Subject(s) - montelukast , rosiglitazone , pharmacokinetics , crossover study , cmax , pharmacology , placebo , dosing , medicine , leukotriene e4 , cyp2c8 , chemistry , endocrinology , leukotriene , cyp3a4 , receptor , metabolism , asthma , alternative medicine , pathology , cytochrome p450
Aims To investigate the effect of multiple dosing with montelukast, a selective leukotriene‐receptor antagonist, on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in humans. Methods A two‐period, randomized crossover study was conducted in 10 healthy subjects. After administration of oral doses of placebo or 10 mg montelukast daily for 6 days, 4 mg rosiglitazone was administered and plasma samples were obtained for 24 h and analyzed for rosiglitazone and N‐desmethylrosiglitazone using high‐performance liquid chromatography with fluorescence detection. Results During the montelukast phase, the total area under the time‐concentration curve (AUC) and peak plasma concentration of rosiglitazone were 102% (90% CI 98, 107%) and 98% (90% CI 92, 103%) of the corresponding values during the placebo phase, respectively. Multiple dosing with montelukast did not affect the oral clearance of rosiglitazone significantly (90% CI 94, 105%; P = 0.50). The AUC ratio and plasma concentration ratios of N‐desmethylrosiglitazone : rosiglitazone were not changed by multiple dosing with montelukast (90% CI 90, 103%; P = 0.14). Conclusions Multiple doses of montelukast do not inhibit CYP2C8‐mediated rosiglitazone metabolism in vivo despite in vitro findings indicating that montelukast is a selective CYP2C8 inhibitor.