Cigarette Smoking Influences Montelukast Pharmacokinetics in Jordanian Population

Rana Said; Rana Abutaima; Basel Arafat; Yasser  Kandil; Lidia Al-Halaseh; Khaldun  Al Azzam; Tawfiq Arafat

doi:10.35516/jjps.v18i3.3216

Authors

Rana Said Pharmacological and Diagnostic Research Centre (PDRC), Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
Rana Abutaima Faculty of Pharmacy, Zarqa University, Zarqa, Jordan
Basel Arafat Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, UK
Yasser I. Kandil Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy, Sinai University–Kantara Branch, Ismailia, Egypt
Lidia K. Al-Halaseh Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mutah University, Al-Karak, Jordan
Khaldun M. Al Azzam Department of Chemistry, School of Science, The University of Jordan, Amman, 11942, Jordan
Tawfiq Arafat Jordan Center for Pharmaceutical Research (JCPR), Amman, Jordan

DOI:

https://doi.org/10.35516/jjps.v18i3.3216

Keywords:

Montelukast Pharmacokinetics, Smoking, Bioequivalence, Singulair®, Montelukast Bioequivalence, Enzyme induction

Abstract

Background: Montelukast is one of the main therapeutic agents used for asthma management. Its therapeutic effectiveness is greatly influenced by the expression of metabolic enzymes and/or transporters involved in its disposition.

Objectives: To assess the effect of smoking on montelukast pharmacokinetics in four bioequivalence studies against the reference drug Singulair^®.

Methodology: Data were extracted from bioequivalence studies to compare 10 mg generic Montelukast to Singulair^® the originator. Primary pharmacokinetic parameters, maximum plasma concentration (C_max) and area under the curve (AUC_0-infand AUC_0-t) were calculated using Kinetica^®. Analysis of Variance was performed to compare montelukast pharmacokinetics between smokers and non-smokers. Statistical significance was set at P ≤ 0.05.

Results: Mean± SD montelukast C_max (ng/mL) was 397.1 ± 125.7 in non-smokers compared to 352.8± 133.9 in smokers. Significant alterations in montelukast C_max (P= 0.0206), AUC _0-t (ng. h/L) 2335 ± 111, P= 0.0016, and AUC _0-inf (ng. h/L) 2509 ± 1163, P= 0.0015 were observed in the study participants who are smokers.

Conclusion: Despite the minimal fold-decrease in montelukast pharmacokinetic parameters in smokers compared to non-smokers, this might have a profound clinical impact on the therapeutic effectiveness of montelukast in patients.

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