Dose linearity testing of intravenous ofloxacin, a novel gyrase inhibitor

After intravenous bolus injection of single doses of 25, 50, 75 and 100 mg of ofloxacin (HOE 280) to 34 healthy male volunteers, concentrations of unchanged drug were estimated at various times in serum and urine over 32 and 48 h. Ofloxacin concentrations were determined using high-pressure liquid chromatography (HPLC). A linear relationship between dose and Cmax (r = 0.91), AUC0-32 (r = 0.95), AUC infinity (r = 0.96) and urinary recovery (r = 0.98) was demonstrated for the doses tested (25-100 mg). The biological half-life (t1/2,beta was determined by fitting a two-compartment open model to the data: t1/2,beta was about 4.5-5.1 h (HPLC, mean values) and was not dose-dependent. Clinically relevant high concentrations of unchanged ofloxacin were detected in urine after the lowest dose (25 mg) for about 24 h, and after the highest dose (100 g) for at least 36 h. General tolerance was good. A slight transient drop in blood pressure was seen after 25 mg in one case; in another, local venous irritation and later restlessness were observed after 75 mg. No specific countermeasures, except for a saline injection into the vein, were needed. All volunteers completed the study as planned.