Abstract
BackgroundMontelukast is a leukotriene receptor antagonist. The release of leukotrienes causes narrowing and constricting in the respiratory airways. Blocking the action of these leukotrienes, montelukast can be used for the prophylaxis and treatment of chronic asthma.ObjectiveThe aim of this study was to evaluate the interchangeability and comparative effectiveness between a generic and a brand montelukast 10 mg immediate release tablets (Broncast® and Singulair®, respectively) after a single oral dose among Arab Mediterranean volunteers.MethodsAn open-label, randomized two-period crossover bioequivalence design was conducted in 31 healthy male volunteers with a 1 week washout between each study period and under fasting conditions. The plasma drug concentration was assessed by using a previously validated LC MS/MS method. The ratio between the generic and brand of geometric least squares means was reported for both generic and brand products. Moreover, an in vitro dissolution study was conducted on generic and brand tablets using three different pH media, and similarity and non-similarity factors (f2 and f1) were calculated.ResultsThe used bioanalytical method was found to be linear within the range 6.098–365.855 ng/mL. The correlation coefficient was close to 0.999 during the course of the study validation. Statistical comparison of the main pharmacokinetic parameters showed the inexistence of any significant difference between generic and the brand. The point estimates (ratios of geometric means) were 111.939, 111.711, and 112.169 % for AUC0–24, AUC0–∞, and Cmax, respectively. The 90 % confidence intervals (CIs) were within the pre-defined limits of 80.00–125.00 % as specified by the FDA and EMA for bioequivalence studies. F2 and f1 were higher than 50 and lower than 15, respectively in all selected pH media.ConclusionBroncast® immediate release film coated tablets (10 mg/tablet) are bioequivalent to Singulair® immediate release film coated tablets (10 mg/tablet), with a comparable safety and efficacy profile. This suggests that these two formulations can be clinically considered interchangeable. The dissolution study suggests that it could be used as premarketing quality control parameter in order to maintain the high quality of the produced product.
Highlights
Bioavailability studies showed that the presence of food in the GIT does not affect bioavailability parameters when an immediate release tablet is given with a standard meal [4, 10]
The method was sufficiently sensitive with lower limit of quantification (LLOQ) of 6.098 ng/ mL and upper limit of quantification (ULOQ) of 609.759 ng/mL
The PK parameter values lie within the EMA and FDA specified bioequivalence limits (80– 125 %) [18, 19]
Summary
The release of leukotrienes causes narrowing and constricting in the respiratory airways. Blocking the action of these leukotrienes, montelukast can be used for the prophylaxis and treatment of chronic asthma. MT is a potent; orally administered and active drug with anti-inflammatory properties that significantly improves asthmatic inflammation factors. It has a great affinity and selectivity to CysLT1 receptors over other respiratory tract receptors; such as the prostanoid; cholinergic; or β-adrenergic receptors. ; it is indicated for the prophylaxis and chronic treatment of asthma in adults and over 1 year-old pediatric patients; and it helps to control the symptoms of seasonal and perennial allergic rhinitis [4, 7, 8]. Bioavailability studies showed that the presence of food in the GIT does not affect bioavailability parameters when an immediate release tablet is given with a standard meal [4, 10]
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