title: Interchangeability and comparative effectiveness between generic and brand montelukast immediate release tablets after a single oral administration in healthy volunteers.
abstract: BACKGROUND
  Montelukast 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.
  
  
  OBJECTIVE
  The 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.
  
  
  METHODS
  An 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Broncast(®) 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.
authors.affiliation: Pharmaceutical Chemistry and Technology, Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, P.O.Box 7, Palestine.
authors.forename: Abdel Naser
authors.initials: AN
authors.lastname: Zaid
authors.affiliation: R&D Department Avalon Pharma (Middle East Pharmaceutical Industries Co. Ltd), Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ayman
authors.initials: A
authors.lastname: Mousa
authors.affiliation: Naratech Pharma Consultancy, Amman, Jordan.
authors.forename: Nadia
authors.initials: N
authors.lastname: Ghazal
authors.affiliation: Pharmaceutical Research Unit, Amman, Jordan.
authors.forename: Rana
authors.initials: R
authors.lastname: Bustami
keywords: Bioequivalence; Efficacy; Immediate release; Montelukast; Safety