Open AccessBioequivalence of the 4‐mg Oral Granules and Chewable Tablet Formulations of Montelukast
Author(s) -
Knorr Barbara,
Hartford Alan,
Li Xiujiang Susie,
Yang Amy Yifan,
Noonan Gertrude,
Migoya Elizabeth
Publication year - 2010
Publication title -
archives of drug information
Language(s) - English
Resource type - Journals
ISSN - 1753-5174
DOI - 10.1111/j.1753-5174.2010.00029.x
Subject(s) - bioequivalence , montelukast , crossover study , pharmacokinetics , medicine , extended release , oral administration , confidence interval , pharmacology , mathematics , alternative medicine , pathology , asthma , placebo
Purpose. The primary objective of the studies was to demonstrate bioequivalence between the oral granules formulation and chewable tablet of montelukast in the fasted state. Effect of food on the pharmacokinetics of the oral granules was also evaluated. Methods. The Formulation Biocomparison Study (Study 1) and the Final Market Image Study (Study 2) each used an open‐label, randomized, 3‐period crossover design where healthy adult subjects (N = 24 and 30, respectively) received montelukast as a single 4‐mg dose of the oral granules formulation and a 4‐mg chewable tablet fasted, and a single 4‐mg dose of the oral granules formulation with food (on 2 teaspoons of applesauce [Study 1] or after consumption of a high‐fat breakfast [Study 2]). The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) for geometric mean ratios (GMRs) (oral granules/chewable tablet) for the AUC 0‐∞ and C max of montelukast were within the prespecified comparability bounds of (0.80, 1.25). For the food‐effect assessment in Study 1, comparability bounds were prespecified as (0.50, 2.00) only for the 90% CI of the GMR (oral granules fed/oral granules fasted) for the AUC 0‐∞ of montelukast; the 90% CI of the GMR for the C max of montelukast, however, also was computed. In Study 2, 90% CIs of the GMRs (oral granules fed/oral granules fasted) for the AUC 0‐∞ and C max of montelukast were computed; comparability bounds were not prespecified. Results. Comparing the exposure of the formulations, the 90% CIs of the GMRs for AUC 0‐∞ and C max were within the prespecified bound of (0.80, 1.25). For AUC 0‐∞ , the GMRs (90% CI) for Study 1 and Study 2 were 1.01 (0.92, 1.11) and 0.95 (0.91, 0.99), respectively. For C max , respective values were 0.99 (0.86, 1.13) and 0.92 (0.84, 1.01). When the oral granules formulation was administered with food, 90% CIs of the GMRs for both AUC 0‐∞ and C max in both studies were contained within the interval of (0.50, 2.00). Conclusions. The 4‐mg oral granules and 4‐mg chewable tablet formulations of montelukast administered in the fasted state are bioequivalent. Single 4‐mg doses of the oral granules formulation and the chewable tablet of montelukast are generally well tolerated.