Purpose: The aim of this study was to assess and compare the pharmacokinetic (PK) properties and bioequivalence of montelukast sodium chewable tablets prepared by two different manufacturers in healthy Chinese volunteers to obtain adequate PK evidence for the registration approval of the test formulation.
Patients and Methods: A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR20182362). Eighteen subjects each were selected for a fasted study and a fed study. Eligible participants were randomly assigned in a 1:1 ratio to receive a single dose of the reference formulation or the test formulation, followed by a 5-day washout period and the administration of the alternate formulation. Plasma samples were collected over a 24-hour period following tablet administration and analyzed for montelukast contents by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The PK parameters, such as maximum serum concentration (C_max), area under the curve (AUC) from t = 0 to the last quantifiable concentration (AUC_0–t), AUC from t = 0 to infinity (AUC_0–∞), half-life (t_1⁄2), time to C_max (T_max), and terminal elimination rate constant (λ_z), were evaluated. The safety assessment included changes in vital signs (blood pressure, pulse, and temperature) or laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis) and the incidence of adverse events (AEs).
Results: The geometric mean ratios (GMRs) between the two formulations for the primary pharmacokinetic parameters (C_max, AUC_{0– 24}, and AUC_0–∞) and the corresponding 90% confidence intervals (Cis) were all within the range of 80.00– 125.00% for both the fasting and fed states. The safety profiles for both treatments were comparable.
Conclusion: The PK analysis revealed that the test and reference formulations of montelukast sodium chewable tablets were bioequivalent and well-tolerated by healthy Chinese subjects.
Keywords: montelukast sodium, bioequivalence, pharmacokinetic profile, HPLC-MS/MS, adverse events