Effect of multiple doses of montelukast on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in humans.
OBJECTIVE
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.
Kim
Kyoung-Ah
KA
Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul, Korea.
Park
Pil-Whan
PW
Kim
Kyong Rae
KR
Park
Ji-Young
JY
D000085:Acetates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004347:Drug Interactions; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077154:Rosiglitazone; D013440:Sulfides; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000085:Acetates; D003521:Cyclopropanes; D007004:Hypoglycemic Agents; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C093875:montelukast