Article date: March 2007
By: Kyoung‐Ah Kim, Pil‐Whan Park, Kyong Rae Kim, Ji‐Young Park, in Volume 63, Issue 3, pages 339-345
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.
DOI: 10.1111/j.1365-2125.2006.02764.x
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