Bioequivalence studies of film-coated tablet and chewable tablet generic formulations of montelukast in healthy volunteers

 

 Buy Article Permissions and Reprints

Abstract

Two studies were conducted in order to assess the bioequivalence of montelukast (CAS 151767-02-1) 10 mg film-coated tablet (FCT) and 5 mg chewable tablet (CT) test formulations in comparison with the original brands. Under fasting conditions, healthy male and female volunteers received one 10 mg FCT or 5 mg CT orally as a single dose of a test or reference formulation. Both studies were designed as open-label, randomized, two-period, two-sequence, crossover studies with a 7-day washout interval. Plasma samples were collected up to 24 h after drug administration and montelukast levels were determined by a validated LC/MS/MS method. Pharmacokinetic parameters were calculated using non-compartmental analysis and were statistically compared by analysis of variance for test and reference formulation. Bioequivalence between products was determined by calculating 90% confidence interval of the ratio test/reference of least-square means of logarithmically transformed C_max and AUC_0–t parameters. AUC_0–∞ was also analysed to obtain additional information. The calculated 90% confidence intervals for the ratios of C_max and AUC_0–t parameters were 89.33–110.52 and 92.06–109.46, respectively, in the FCT study, and 91.58–101.86 and 92.15–98.83, respectively, in the CT study, which are all within the bioequivalence acceptance range of 80–125%. Based on the results, it can be concluded that the evaluated test FCT and CT formulations are bioequivalent to their respective reference formulation in terms of rate and extent of absorption.

• References

• 1 Reiss TF, Chervinsky P, Dockhorn RJ, Shingo S, Seidenberg B, Edwards TB. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma. Arch Intern Med. 1998; 158: 1213-20
  CrossrefPubMedGoogle Scholar
• 2 Merck Pharmaceuticals Summary of Product Characteristics Singulair 10 mg. Merck Sharp & Dohme de España. Madrid. April 2010.
  PubMed
• 3 The electronic Medicines Compendium (eMC) [Internet]. http://www.medicines.org.uk Accessed on 04/02/2011.
  PubMed
• 4 Leff IA Busse WW, Pearlman D, Bronsky EA, Kemp J, Hen-deles L et al. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med. 1998; 339: 147-52
  CrossrefPubMedGoogle Scholar
• 5 Philip G, Villarán C, Pearlman DS, Loeys T, Dass SB, Reiss TF. Protection against exercise-induced bronchoconstriction two hours after a single oral dose of montelukast. J Asthma. 2007; 44: 213-17
  CrossrefPubMedGoogle Scholar
• 6 Pearlman DS, van Adelsberg J, Philip G, Tilles SA, Busse W, Hendeles L et al. Onset and duration of protection against exercise-induced bronchoconstriction by a single oral dose of montelukast. Ann Allergy Asthma Immunol. 2006; 97: 98-104
  CrossrefPubMedGoogle Scholar
• 7 Merck Pharmaceuticals Summary of Product Characteristics Singulair 5 mg. Merck Sharp & Dohme de España. Madrid. April 2010.
  PubMed
• 8 PDR Network [Internet], http://www.pdr.net Accessed on 04/02/2011.
  PubMed
• 9 Jarvis B, Markham A. Montelukast: a review of its therapeutic potential in persistent asthma. Drugs. 2000; 59: 891-928
  CrossrefPubMedGoogle Scholar
• 10 Blake KV. Montelukast: data from clinical trials in the management of asthma. Ann Pharmacother. 1999; 33: 1299-314
  CrossrefPubMedGoogle Scholar
• 11 Stohlmeyer LA. Montelukast: a new medication for pediatric asthma management. J Pediatr Health Care. 1998; 12: 324-8
  CrossrefPubMedGoogle Scholar
• 12 Canadian Pharmacists Association. Compendium of Pharmaceuticals and Specialties. Summary Product Information Singulair®.
  PubMed
• 13 Chiba M, Xu X, Nishime JA, Balani SK, Lin JH. Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans. Drug Metab Dispos. 1997; 25: 1022-31
  PubMedGoogle Scholar
• 14 CPMP (Committee for Proprietary Medicinal Products): Guideline on the Investigation of Bioequivalence. London 2010.
  PubMed
• 15 Good Clinical Practice Consolidated Guideline, International Conference on Harmonisation, E6. 1996.
  PubMed
• 16 Markham A, Faulds D. Montelukast. Drugs. 1998; 56: 251-56
  CrossrefPubMedGoogle Scholar
• 17 Knorr B, Holland S, Rogers JD, Nguyen HH, Reiss TF. Montelukast adult (10-mg film-coated tablet) and pediatric (5-mg chewable tablet) dose selections. J Allergy Clin Immunol. 2000; 106: S171-8
  CrossrefPubMedGoogle Scholar
• 18 Amin RD, Cheng H, Rogers JD. Determination of MK-0476 in human plasma by liquid chromatography. J Pharm Biomed Anal. 1995; 13: 155-8
  CrossrefPubMedGoogle Scholar