Dose linearity and other pharmacokinetics of ofloxacin: a new, broad-spectrum antimicrobial agent

After oral administration of a single dose of ofloxacin (100, 300 or 600 mg) to 13 healthy male volunteers in an open, randomized crossover study, concentrations of the unchanged drug were estimated at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dose was followed by a wash-out period of 1 week. Ofloxacin concentrations were determined using both high pressure liquid chromatography (HPLC) and a microbiological assay. The measurements obtained were compared by linear distribution independent regression, and were found to be equivalent, indicating no major metabolism of ofloxacin. Maximum serum concentrations (Cmax) of ofloxacin after administration of 100, 300 or 600 mg were, respectively, 1.0, 3.4 and 6.9 mg/ml (HPLC, median values). A linear relationship between Cmax and dose was demonstrated within the range tested (coefficient of correlation r = 0.88). The same applied to AUC0-28 (r = 0.98) and to urinary recovery of the drug (r = 0.98). Time to reach Cmax varied between 0.5 and 1.1 hours (median values), indicating rapid absorption of the drug. Biological half-life (t1/2 beta) was determined by fitting a two-compartment open model to the date: t1/2 beta was in the range 5.6 to 6.4 hours (HPLC, median values) and was not relevantly dose-dependent. Urinary concentrations of ofloxacin remained above 1 microgram/ml, i.e. above the minimum inhibitory concentrations (MIC90) for most bacterial strains at all dosages tested, for at least 36 hours after drug administration. General tolerability was good; no side-effects were reported.