Bioavailability of Two Oral-Granule Formulations of a Single Dose of 4-Mg Oral Granules of Montelukast: A Randomized, Two-Period Crossover Comparison in Healthy Mexican Adult Volunteers

Abstract

Montelukast is a leukotriene receptor antagonist. In Mexico, the oral granules at the dose of 4 mg are indicated for children aged 6 months to 5 years for the treatment of asthma and/or allergic rhinitis. The aim of this study was to compare the bioavailability and to determine the bioequivalence of a test formulation (oral granules) containing 4 mg of montelukast, with its corresponding reference drug formulation, and to generate data regarding the oral bioavailability of this drug in the Mexican population. This single-dose, randomized-sequence, single-blind, twoperiod crossover study under fasting conditions was conducted on a total of 26 healthy Mexican adult subjects of both genders , with a seven-day washout period. Study formulations were administered after a 10-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12 and 24 hours after administration. Plasma concentrations of montelukast were determined using HPLC coupled to a mass spectrometry (MS/MS) detector. The test and reference formulations were considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%. The 90% CIs for montelukast Cmax, AUC0–t and AUC0–∞ were 97.57% to 109.35%, 101.81% to 108.92%, and 101.55% to 109.96%, respectively. In this study a single dose of the test formulation met the regulatory requirements for assuming bioequivalence, based on the rate and extent of absorption.