PHARMACOKINETICS OF FLUMEQUINE IN SHEEP AFTER INTRAVENOUS AND INTRAMUSCULAR ADMINISTRATION - BIOAVAILABILITY AND TISSUE RESIDUE STUDIES

The pharmacokinetic properties of flumequine and its metabolite 7-hydr oxy-flumequine were determined in six healthy sheep after single intra muscular (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 a fter repeated i.m. administration with a first dose of 12 mg/kg and ni ne 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 phas e. 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 compartm ent with a slow rate of return to the central compartment. The mean el imination half-life was 11.5 h. The 7-hydroxyflumequine plasma levels represented 2.3 % of the total area under the curve. The mean plasma c oncentrations of flumequine after i.m. administration were characteris tic of a two-compartment model with a first order absorption. The mean maximal plasma concentration (1.83 +/- 1.15 mu g/mL) was obtained rap idly, 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 mi nimal concentrations of flumequine during repeated treatment were sign ificantly lower in females than in males. Eighteen hours after the las t repeated i.m. administration, the highest concentration of flumequin e was observed at the injection sites followed by kidney, liver, muscl e and fat. The highest concentration of 7-hydroxyflumequine was observ ed in the kidney and was ten times lower than the flumequine concentra tion. The longest flumequine elimination half-life was observed in the fat.