Bioequivalence studies for two different strengths of montelukast in healthy volunteers: 10 mg film-coated tablets and 5 mg chewable tablets

摘要

In order to assess the bioequivalence of 2 different formulations of montelukast, a pivotal trial for the montelukast 10 mg film-coated tablets formulation and a pivotal trial for the montelukast 5 mg chewable tablets formulation were conducted. For the 10 mg study, 34 healthy subjects were enrolled in a single centre, randomised, single-dose, open-label, 2-way crossover study, with a minimum washout period of 7 days, while for the 5 mg study, 42 healthy subjects were included in another study with a similar design. For both studies, plasma samples were collected up to 24 h post-dosing and drug levels were determined by reverse liquid chromatography and detected by tandem mass spectrometry detection. Pharmacokinetic parameters used for bioequivalence assessment, area under the concentration-time curve from time zero to time of last non-zero concentration (AUC0-t) and from time zero to infinity (AUC0-inf) and maximum observed concentration (Cmax), were determined from the drug concentration data using non-compartmental analysis. In the 10 mg study, the 90% confidence intervals obtained by analysis of variance were 99.62-120.51% for Cmax, 102.25-117.37% for AUC 0-t and 101.96-116.67% for AUC0-inf, which were within the predefined acceptable range of 80.00-125.00%. In the 5 mg study, the 90% confidence intervals were 91.14-98.46% for Cmax, 93.02-98.42% for AUC0-t and 93.09-98.63% for AUC0-inf, which were within the predefined acceptable range of 80.00-125.00%. Bioequivalence between formulations was concluded both in terms of rate and extent of absorption for both strengths.