Pharmacokinetics and bioequivalence study of montelukast sodium oral soluble film and chewable tablet in healthy Chinese volunteers: randomized trials under fasting and fed conditions.

Abstract

The oral soluble film (OSF) is a new drug delivery system. Whether montelukast sodium OSF has similar pharmacokinetic (PK) properties and bioequivalence to chewable tablet (CT) should be investigated. This study, conducted at Haikou People's Hospital, consisted of two trials: a randomized, open-label, single-dose, 3-sequence, 3-period crossover trial under fasting conditions and a randomized, open-label, single-dose, 2-sequence, 2-period crossover trial under fed conditions. Healthy volunteers were randomized 1:1:1 to receive single-dose oral montelukast sodium OSF without water, OSF, or CT with water in the fasting trial, and 1:1 to receive OSF or CT with water in the fed trial in each period, with a 7-day washout period. Randomization was performed according to random number tables generated using computer. Blood samples were collected over a 24-h period. Plasma drug concentrations were tested using high-performance liquid chromatography-tandem mass spectrometry. The primary PK parameters were maximum plasma drug concentration (Cmax), area under the plasma drug concentration-time curve (AUC) from t=0 to the last quantifiable concentration (AUC0-t), and AUC from t=0 to infinity (AUC0-∞). The other PK parameters included time to Cmax (Tmax), terminal elimination rate constant (λz), and half-life (t1/2). Safety was also assessed. Analysis of variance on log-transformed primary PK parameters was applied to analyze the bioequivalence between the OSF and CT. The bioequivalence margin was 80-125%. From November 2018 to January 2019, 30 subjects were included in each trial. The PK parameters between OSF and CT were numerically similar. All 90% confidence intervals (CIs) of the geometric mean ratio (GMR) for the primary PK parameters fell within 80-125%, confirming the bioequivalence of montelukast sodium OSF and CT under fasting and fed conditions. In the fasting trial, 6 (20%) adverse events (AEs) were reported, including 3 (10%) cases after OSF administration without water and 3 (10%) after OSF administration with water, with no serious AEs. No AEs were recorded in the fed trial. Montelukast sodium OSF is bioequivalent to CT, with acceptable safety. The OSF is an alternative option of CT. ClinicalTrials.gov identifiers: NCT05528198 (the fasting trial) and NCT05531994 (the fed trial).