Characterization of the pharmacokinetic disposition of levofloxacin in stallions after intravenous and intramuscular administration

The target of the present study was to investigate the plasma disposition kinetics of levofloxacin in stallions (n = 6) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injection at a dose rate of 4 mg/kg bwt, using a two-phase crossover design with 15 days as an interval period. Plasma samples were collected at appropriate times during a 48-h administration interval, and were analyzed using a microbiological assay method. The plasma levofloxacin disposition was best fitted to a two-compartment open model after i.v. dosing. The half-lives of distribution and elimination were 0.21 +/- 0.13 and 2.58 +/- 0.51 h, respectively. The volume of distribution at steady-state was 0.81 +/- 0.26 L/kg, the total body clearance (Cl-tot) was 0.21 +/- 0.18 L/h/kg, and the areas under the concentration-time curves (AUCs) were 18.79 +/- 4.57 mu g.h/mL. Following i.m. administration, the mean t(1/2el) and AUC values were 2.94 +/- 0.78 h and 17.21 +/- 4.36 mu g.h/mL. The bioavailability was high (91.76% +/- 12.68%), with a peak plasma mean concentration (C-max) of 2.85 +/- 0.89 mu g/mL attained at 1.56 +/- 0.71 h (T-max). The in vitro protein binding percentage was 27.84%. Calculation of efficacy predictors showed that levofloxacin might have a good therapeutic profile against Gram-negative and Gram-positive bacteria, with an MIC <= 0.1 mu g/mL.