Disposition kinetics and pharmacokinetics-pharmacodynamic integration of difloxacin against Staphylococcus aureus isolates from rabbits

The pharmacokinetics of difloxacin were studied following intravenous (IV), subcutaneous (SC) and oral administration of 5 mg/kg to healthy white New Zealand rabbits (n = 6). Difloxacin concentrations were determined by HPLC assay with fluorescence detection. Minimal inhibitory concentrations (MICs) assay of difloxacin against different strains of S. aureus from different european countries was performed in order to compute the main pharmacodynamic surrogate markers. The plasma difloxacin clearance (Cl) for the IV route was (mean +/- SD) 0.41 +/- 0.05 L/h kg. The steady-state volume of distribution (V-ss) was 1.95 +/- 0.17 L/kg. The terminal half-life (t(1/2 lambda z)) was (mean +/- SD) 4.19 +/- 0.34 h, 7.53 +/- 1.32 h and 8.00 +/- 0.45 after IV, IM and oral, respectively. From this data, it seems that a 5 mg/kg dose difloxacin would be effective by SC and oral routes in rabbits against bacterial isolates with MIC <= 0.1 mu g/mL. (C) 2007 Elsevier Ltd. All rights reserved.