Bioavailability and pharmacokinetics of oral ofloxacin formulations in normal subjects

The relative bioavailability and pharmacokinetics of ofloxacin tablets and a reference oral solution of ofloxacin were compared in 32 normal male subjects using a randomized two-way crossover design. After an overnight fast, subjects were randomized to receive a single 200 mg or 300 mg dose of ofloxacin (tablet or solution) and blood samples were obtained prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours after the dose. After a 5-day wash-out period, subjects were administered the same dose but of the other formulation, and blood samples were collected in an identical manner. Plasma concentrations of ofloxacin were determined by high-pressure liquid chromatography. The results showed that ofloxacin tablets were more slowly absorbed when compared to the solution and mean peak plasma concentrations were obtained in about 1.5 hours for the tablet preparation. Maximum plasma concentrations were higher after administration of the solution (Cmax = 2.24 micrograms/ml, 200 mg; Cmax = 3.25 micrograms/ml, 300 mg) compared to the tablet (Cmax = 1.74 micrograms/ml, 200 mg; 2.61 micrograms/ml, 300 mg). The bioavailability of ofloxacin tablets was greater than 98% compared to the solution. The other pharmacokinetic parameters were similar between the two dosage formulations. Ofloxacin tablets revealed an apparent volume of distribution of 1.5 l/kg, an elimination half-life of 5.6 hours, and a total clearance of 251 ml/min. In addition, a linear increase in plasma concentrations was observed when the dose of ofloxacin was increased. In summary, ofloxacin tablets was found to be reliably bioavailable and bioequivalent to the reference solution.