Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults

Montelukast is an effective and well-tolerated treatment for the prophylaxis and chronic treatment of asthma, acute prevention of exercise-induced bronchoconstriction and symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. The aim of the study was to compare bioavailability, and characterise the pharmacokinetic profile and safety of Sandoz generic montelukast 4 mg oral granules relative to Singulair^® mini (Merck, Sharp & Dohme). An open-label, randomised, single-dose, two-treatment, two-period, two-sequence, two-way crossover bioequivalence study was conducted in healthy male volunteers aged 18–55 years, under fasting conditions. The duration of the clinical part of the trial was ≈ 11 days. Montelukast levels in plasma were quantified using a validated liquid chromatography tandem mass spectrometry method, and pharmacokinetic parameters calculated from the drug concentration–time profile using a non-compartmental model. A total of 40 subjects completed both study periods. The ratio test/reference of geometric least squares means was calculated for both formulations of montelukast for the In-transformed pharmacokinetic parameters; the 90% confidence intervals (CIs) were within the pre-defined limits of 80.00–125.00%: 92.2% (90% CI: 87.42–97.30%) for C_max, 98.1% (90% CI: 94.49–101.81%) for AUC_0–t and 97.6% (90% CI: 94.14–101.27%) for AUC_0–∞. Two study subjects each reported one mild adverse event: dyspepsia (possibly related to study medication) and throat pain (not considered related to study medication). Sandoz montelukast 4 mg oral granules are bioequivalent to Singulair^® 4 mg mini oral granules, with a similar safety profile. This suggests that these two preparations can be considered interchangeable in clinical practice.