Abstract
The pharmacokinetics of difloxacin (Dicural) was studied in a crossover study using three groups (n = 4) of male and female Friesian calves after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations of 5 mg/kg body weight. Drug concentration in plasma was determined by high-performance liquid chromatography using fluorescence detection. The plasma concentration-time data following i.v. administration were best fitted to a two-compartment open model and those following i.m. and s.c. routes were best fitted using one-compartment open model. The collected data were subjected to a computerized kinetic analysis. The mean i.v., i.m. and s.c. elimination half-lives (t(1/2beta)) were 5.56 +/- 0.33 h, 6.12 +/- 0.42 h and 7.26 +/- 0.6 h, respectively. The steady-state volume of distribution (V(dss)) was 1.12 +/- 0.09 L/kg and total body clearance (Cl(B)) was 2.19 +/- 0.1 ml/(min x kg). The absorption half lives (t(1/2ab)) were 0.38 +/- 0.027 h and 2.1 +/- 0.09 h, with systemic bioavailabilities (F) of 96.5% +/- 6.4% and 84% +/- 5.5% after i.m. and s.c. administration, respectively. After i.m. and s.c. dosing, peak plasma concentrations (C(max)) of 3.38 +/- 0.13 microg/ml and 2.18 +/- 0.12 microg/ml were attained after (t(max)) 1.22 +/- 0.20 h and 3.7 +/- 0.52 h. The MIC90 of difloxacin for Mannheimia haemolytica was 0.29 +/- 0.04 microg/ml. The AUC/MIC90 and C(max)/MIC90 ratios for difloxacin following i.m. administration were 120 and 11.65, respectively and following s.c. administration were 97.58 and 7.51, respectively. Difloxacin was 31.7-36.8% bound to calf plasma protein. Since fluoroquinolones display concentration-dependent activities, the doses of difloxacin used in this study are likely to involve better pharmacodynamic characteristics that are associated with greater clinical efficacy following i.m. administration than following s.c. administration.