Two open-label, randomized, crossover studies assessing the bioequivalence of ofloxacin administered as immediate-and extended-release formulations in healthy subjects

Abstract

Background: Ofloxacin is a fluoroquinolone agent available as an immediate-release (IR) tablet formulation administered twice daily. An extended-release (ER) formulation of ofloxacin has been developed for oncedaily administration.

Objectives: The present studies compared the pharmacokinetic (PK) and safety profiles of the ER and IR formulations of ofloxacin.

Methods: Based on specific inclusion and exclusion criteria, healthy adult male and female volunteers were selected to receive single and multiple oral doses of ofloxacin ER 400 mg QD and ofloxacin IR 200 mg BID in 2 separate open-label, randomized, crossover studies. Multiple blood samples were collected, and plasma concentrations of ofloxacin were analyzed using a high-throughput liquid chromatography system. PK parameters were calculated using noncompartmental methods. Safety was assessed in the clinical pharmacology unit based on vital signs, electrocardiograms (ECGs), and reported adverse events. The relationship of an adverse event to study drugs (definitely, probably, possibly, remotely, or unrelated) was assessed by the principal investigator.

Results: Forty healthy subjects were included in each study. Thirty-seven subjects (28 men, 9 women; mean age, 37 years; mean weight, 71.2 kg) completed the single-dose study, and 38 subjects (33 men, 5 women; mean age, 36 years; mean weight, 72.2 kg) completed the multiple-dose study. With the exception of 3 black subjects in each study of African-American origin, all subjects in both studies were white. The mean AUC(0-24) values for the ER formulation in the single-and multiple-dose studies (18.6 and 21.4 mg . h/L, respectively) were similar to those for the IR formulation (17.7 and 22.8 mg x h/L), with the 90% CIs falling between 80.0 and 125.0. Mean C(max) values for the ER formulation in the single- and multiple-dose studies (2.02 and 2.12 mg/L) were also similar to those for the IR formulation (1.74 and 1.85 mg/L). Under steady-state conditions, median T(max) values for the ER formulation were significantly longer than those for the IR formulation (5.00 vs 2.00 hours, respectively; P < 0.05). All vital signs and ECGs were within normal ranges during the single- and multipledose studies. Adverse events probably related to study drugs (eg, nausea, loose stools, emesis) were similar in nature and frequency between the 2 formulations. No serious adverse events were reported during either study.

Conclusion: In these 2 trials in a selected group of healthy adult male and female volunteers, the ER and IR formulations of ofloxacin displayed a similar rate and extent of bioavailability and comparable safety profiles.