Average Bioequivalence Of Single 500 Mg Doses Of Two Oral Formulations Of Levofloxacin: A Randomized, Open-label, Two-period Crossover Study In Healthy Adult Brazilian Volunteers

摘要

Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(C) (Sanofi-Aventis Farmaceutica Ltda, Brazil, reference product) and Levaquin(C) (Janssen-Cilag Farmaceutica Ltda, Brazil, test product) was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters C-max, T-max, K-el, T-1/2el, AUC(0-t) and AUC(0-inf) were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI) for the ratio of C-max, AUC(0-t) and AUC(0-inf) values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for C-max, AUC(0-t) and AUC(0-inf) were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(C) and Levaquin(C) are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.