Safety and pharmacokinetics of single dose intravenous ofloxacin in healthy volunteers

Abstract

The safety and pharmacokinetics of single dose intravenous ofloxacin were studied in 32 healthy male volunteers participating in a single-centre, two-protocol, randomized, crossover double-blind, placebo-controlled study. Ofloxacin (50, 100, or 200 mg in protocol 1 or 200 or 400 mg in protocol 2) or a placebo was administered as a single 1-h infusion. Ofloxacin plasma and urine concentrations were measured using high-performance liquid chromatography. Statistically significant but clinically insignificant dose-dependency in ofloxacin pharmacokinetics over the dosage range of 50 to 200 mg was evidenced by increases in dose-normalized area under the plasma concentration-versus-time curve (mean +/- s.d., 2.47 +/- 0.40 to 3.05 +/- 0.44 mg/L.h per 50 mg) and terminal disposition half-life (harmonic mean 4.49 to 5.29 h) and a decline in total body clearance (20.68 +/- 3.13 to 16.67 +/- 2.21 L/h) as the dose increased. High volume of distribution (means of 121 to 135 L) suggested effective extravascular distribution. High total (means of 16 to 21 L/h) and renal (means of 9 to 11 L/h) clearances indicated primarily renal elimination of the compound via glomerular filtration and tubular secretion. There were no significant differences between the ofloxacin and placebo groups in either protocol in the proportion of subjects reporting adverse experiences. Further pharmacokinetic and clinical studies with intravenous ofloxacin are warranted.