Pharmacokinetics of intravenous and oral enoxacin in healthy volunteers

Abstract

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.

Distribution kinetics of enoxacin and its metabolite oxoenoxacin in excretory fluids of healthy volunteers

“…The results for the basic pharmacokinetic parameters of enoxacin and oxoenoxacin obtained in this study are in good agreement with those of other authors (7,39). The concentrations of enoxacin in plasma are above the MIC at which 90% of sensitive pathogens are inhibited (31,44).…”

“…Its pharmacokinetics in healthy volunteers was studied by several investigators (7,39,43). The apparent volume of distribution of enoxacin, like that of other gyrase inhibitors, exceeds the body volume by two-to threefold, suggesting extensive localization at intracellular sites.…”

Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole

“…This difference does not seem to be of clinical relevance, because there were no significant differences concerning the most important parameters, such as the AUC and clearance. The data are in good agreement with the results of others (7,21,25,31,37,42,45).…”

“…Enoxacin is available as an oral and parenteral drug characterized by a high bioavailability, a good tissue penetration after oral administration, and an antibacterial spectrum similar to that of fleroxacin (6). In contrast to fleroxacin, twice-daily administration is necessary because of the shorter half-life (7).…”

Quinolones: a class of antimicrobial agents

“…Upon multiple dosing, ciprofloxacin, enoxacin and other fluoroquinolones have shown an increase in the t 1/2 and increased V d from the first dose (Chang et al, 1988;Nix and Schentag, 1988); however, this phenomenon was not observed for norfloxacin in dogs using a dosage regimen of 5 mg/ kg every 12 h for 14 days (Brown et al, 1990) nor for ciprofloxacin in other studies (Höffler et al, 1984;Drusano et al, 1986) nor in dogs (Abadía et al, 1994b). The area under the concentration time curve normalized to a 1 mg/kg dose decreased as the dose of norfloxacin increased from 5 mg/kg to 20 mg/kg in healthy dogs (Brown et al, 1990).…”