Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration: Bioavailability and tissue residue studies

The pharmacokinetic properties of flumequine and its metabolite 7-hydroxy-flumequine were determined in six healthy sheep after single intramuscular (i.m.) and intravenous (i.v) injections at a dose of 6 mg/kg body weight. The tissue residues were determined in 20 healthy sheep after repeated i.m. administration with a first dose of 12 mg/kg and nine doses of 6 mg/kg. The flumequine formulation used was Flumiquil 3% Suspension Injectable(R). The mean plasma concentrations of flumequine after i.v. administration were described by a three-compartment open model with a rapid distribution and a relatively slow elimination phase. The low value of volume of distribution at steady state (V-dss) (0.52 +/- 0.24 L/kg) and high value of volume of distribution (V-d lambda(3)) (5.05 +/- 3.47 L/kg) emphasized the existence of a small compartment with a slow rate of return to the central compartment. The mean elimination half-life was 11.5 h. The 7-hydroxyflumequine plasma levels represented 2.3 % of the total area under the curve. The mean plasma concentrations of flumequine after i.m. administration were characteristic of a two-compartment model with a first order absorption. The mean maximal plasma concentration (1.83 +/- 1.15 mu g/mL) was obtained rapidly, i.e. 1.39 +/- 0.71 h after the i.m, administration. The fraction of dose absorbed from the injection site was 85.00 +/- 30.13%. The minimal concentrations of flumequine during repeated treatment were significantly lower in females than in males. Eighteen hours after the last repeated i.m. administration, the highest concentration of flumequine was observed at the injection sites followed by kidney, liver, muscle and fat. The highest concentration of 7-hydroxyflumequine was observed in the kidney and was ten times lower than the flumequine concentration. The longest flumequine elimination half-life was observed in the fat.