Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method

Abdel Naser Zaid, Murad N Abualhasan, David G Watson, Ayman Mousa, Nadia Ghazal, Rana Bustami

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 (R2) 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 Cmax, 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.
LanguageEnglish
Pages5315-5321
Number of pages7
JournalDrug Design, Development and Therapy
Volume9
DOIs
Publication statusPublished - 23 Sep 2015

Fingerprint

montelukast
Therapeutic Equivalency
Tablets
Oral Administration
Pediatrics
Rhinitis, Allergic, Perennial
Generic Drugs
Leukotrienes
Tandem Mass Spectrometry
Least-Squares Analysis
Pharmaceutical Preparations
Area Under Curve
Volunteers
Fasting
Healthy Volunteers
Asthma
Medicine

Keywords

  • bioequivalence
  • chewable
  • efficacy
  • montelukast
  • safety

Cite this

Zaid, Abdel Naser ; Abualhasan, Murad N ; Watson, David G ; Mousa, Ayman ; Ghazal, Nadia ; Bustami, Rana. / Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method. In: Drug Design, Development and Therapy. 2015 ; Vol. 9. pp. 5315-5321.
@article{6df4a0c78aff4ac8999a3c663df47832,
title = "Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method",
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{\circledR} 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 (R2) 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 Cmax, 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{\circledR} pediatric chewable tablets (5 mg/tablet) are bioequivalent to Singulair{\circledR} pediatric chewable tablets (5 mg/tablet), with a similar safety profile. This suggests that these two formulations can be considered interchangeable in clinical practice.",
keywords = "bioequivalence, chewable, efficacy, montelukast, safety",
author = "Zaid, {Abdel Naser} and Abualhasan, {Murad N} and Watson, {David G} and Ayman Mousa and Nadia Ghazal and Rana Bustami",
year = "2015",
month = "9",
day = "23",
doi = "10.2147/DDDT.S87938",
language = "English",
volume = "9",
pages = "5315--5321",
journal = "Drug Design, Development and Therapy",
issn = "1177-8881",

}

Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method. / Zaid, Abdel Naser; Abualhasan, Murad N; Watson, David G; Mousa, Ayman; Ghazal, Nadia; Bustami, Rana.

In: Drug Design, Development and Therapy, Vol. 9, 23.09.2015, p. 5315-5321.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method

AU - Zaid, Abdel Naser

AU - Abualhasan, Murad N

AU - Watson, David G

AU - Mousa, Ayman

AU - Ghazal, Nadia

AU - Bustami, Rana

PY - 2015/9/23

Y1 - 2015/9/23

N2 - 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 (R2) 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 Cmax, 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.

AB - 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 (R2) 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 Cmax, 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.

KW - bioequivalence

KW - chewable

KW - efficacy

KW - montelukast

KW - safety

UR - http://www.scopus.com/inward/record.url?scp=84942741309&partnerID=8YFLogxK

U2 - 10.2147/DDDT.S87938

DO - 10.2147/DDDT.S87938

M3 - Article

VL - 9

SP - 5315

EP - 5321

JO - Drug Design, Development and Therapy

T2 - Drug Design, Development and Therapy

JF - Drug Design, Development and Therapy

SN - 1177-8881

ER -