The disposition kinetics of difloxacin, a fluoroquinolone antibiotic, after intravenous (IV), intramuscular (IM) and subcutaneous (SQ administration were determined in sheep at a single dose of 5 mg/kg. The concentration-time data were analysed by compartmental (after IV dose) and non-compartmental pharmacokinetics method (after IV, IM and SC administration). Plasma concentrations of difloxacin were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution (V-ss) and clearance (CI) of difloxacin after IV administration were 1.68 +/- 0.21 L/kg and 0.21 +/- 0.03 L/h kg, respectively. Following IM and SC administration difloxacin achieved maximum plasma concentration of 1.89 +/- 0.55 and 1.39 +/- 0.14 mg/L at 2.42 +/- 1.28 and 5.33 +/- 1.03 h, respectively. The absolute bioavailabilities after IM and SC routes were 99.92 +/- 26.50 and 82.35 +/- 25.65%, respectively. Based on these kinetic parameters, difloxacin is likely to be effective in sheep. (C) 2007 Elsevier Ltd. All rights reserved.