Abstract
BACKGROUND: Montelukast (MT) is a leukotriene D4 antagonist. It is an effective and safe medicine for the prophylaxis and treatment of chronic asthma. It is also used to prevent acute exercise-induced bronchoconstriction and as a symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. OBJECTIVE: The aim of this study was to evaluate the bioequivalence (BE) of two drug products: generic MT 5 mg chewable tablets versus the branded drug Singulair(®) pediatric 5 mg chewable tablets among Mediterranean volunteers. METHODS: An open-label, randomized two-period crossover BE design was conducted in 32 healthy male volunteers with a 9-day washout period between doses and under fasting conditions. The drug concentrations in plasma were quantified by using a newly developed and fully validated liquid chromatography tandem mass spectrometry method, and the pharmacokinetic parameters were calculated using a non-compartmental model. The ratio for generic/branded tablets using geometric least squares means was calculated for both the MT products. RESULTS: The relationship between concentration and peak area ratio was found to be linear within the range 6.098-365.855 ng/mL. The correlation coefficient (R (2)) was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between the generic and branded products. The point estimates (ratios of geometric means) were 101.2%, 101.6%, and 98.11% for area under the curve (AUC)0→last, AUC0→inf, and C max, respectively. The 90% confidence intervals were within the predefined limits of 80.00%-125.00% as specified by the US Food and Drug Administration and European Medicines Agency for BE studies. CONCLUSION: Broncast(®) pediatric chewable tablets (5 mg/tablet) are bioequivalent to Singulair(®) pediatric chewable tablets (5 mg/tablet), with a similar safety profile. This suggests that these two formulations can be considered interchangeable in clinical practice.