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A Comparative Multidose Pharmacokinetic Study of Buspirone Extended‐Release Tablets with a Reference Immediate‐Release Product
Author(s) -
Sakr Adel,
Andheria Mahalaxmi
Publication year - 2001
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700122010681
Subject(s) - buspirone , pharmacokinetics , bioavailability , crossover study , pharmacology , active metabolite , steady state (chemistry) , bioequivalence , immediate release , medicine , chemistry , agonist , placebo , receptor , alternative medicine , pathology
Buspirone is disclosed in U.S. Patent No. 3,717,634 as a pharmaceutically active compound that has been found to be effective for the treatment of anxiety disorders and depression. In this randomized, two‐treatment, two‐period, multidose crossover study, the pharmacokinetics of a once‐daily extended‐release (ER) formulation of buspirone was compared with that of an immediate‐release (IR) formulation of commercially available buspirone. A total of 30 mg of the ER formulation was administered to 36 healthy volunteers once daily for 7 days, and 15 mg of the IR formulation was administered twice daily for 7 days. Pharmacokinetic profiles of buspirone and its metabolite, 1‐pyrimidinylpiperazine (1‐PP), were obtained at steady state. The bioavailability of buspirone from the ER formulation was more than three times higher than that from the IR formulation at steady state, and that of 1‐PP was about 25% less. The mean steady‐state C max of buspirone from the ER formulation was 46% higher than that from the IR formulation (p < 0.05), and that for 1‐PP was lower by 29% (p < 0.05). The mean apparent half‐life of buspirone from the ER formulation (9.04 hours) was considerably longer than that observed for the IR formulation (3.06 hours). The median 1‐PP/buspirone AUC ratio was much higher for the IR formulation at steady state (24.4) than for the ER formulation (6.44). There were no significant differences in average pharmacokinetic metrics observed in men and women. Based on these observations of the potential benefits of once‐daily dosing with the ER product in terms of prolonged buspirone plasma concentrations, a significant in‐crease in the ratio of buspirone to 1‐PP concentration with a lower intersubject variation could be achieved that should provide an improvement in the desired therapeutic effects of buspirone .