Cigarette Smoking Influences Montelukast Pharmacokinetics in Jordanian Population

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 (Cmax) and area under the curve (AUC0-inf and AUC0-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 Cmax (ng/mL) was 397.1 ± 125.7 in non-smokers compared to 352.8± 133.9 in smokers. Significant alterations in montelukast Cmax (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.