Pharmacokinetics of intravenous and oral enoxacin in healthy volunteers.

In a randomized, crossover study single 200 and 800 mg doses of enoxacin were administered intravenously and orally to eight healthy normal volunteers. Plasma and urinary enoxacin concentrations and urinary concentrations of its oxo-metabolite were determined by high-performance liquid chromatography. At the end of a 1 h intravenous infusion period, mean enoxacin plasma concentrations were 1.8 and 6.6 mg/l for the 200 and 800 mg doses, respectively. Disappearance of enoxacin from the systemic circulation appeared to follow first order kinetics with harmonic mean elimination half lives of 3.3 and 4.7 h for the 200 and 800 mg dose groups, respectively. However, enoxacin kinetics were dose-dependent over the dose range tested. Total body clearance decreased and elimination half-life increased with increasing dose. The volume of distribution was large (2.8 l/kg) and independent of dose. Absorption of orally administered enoxacin was rapid, with mean peak plasma concentrations (1.0 and 3.8 mg/l) appearing one to two hours postdose. Absolute oral bioavailability averaged 89%, and was independent of the dose administered. Cumulative enoxacin urinary recovery accounted for 51-53% of the dose irrespective of dose or route of administration. Enoxacin renal clearance exceeded creatinine clearance indicating that urinary excretion of enoxacin involved both glomerular filtration and tubular secretion. Urinary excretion of the oxo-metabolite averaged 16% and 11% following the 200 and 800 mg dose, respectively. Evidence of dose dependent decrease in enoxacin renal clearance and formation of its oxo-metabolite was observed. Enoxacin was well tolerated during the course of the trial. The present study shows that enoxacin pharmacokinetics can be characterized by apparent first order elimination, large volume of distribution, and dose-dependent increase of half life. Oral absorption of enoxacin is complete over a wide dose range.