Single dose pharmacokinetic study of flumequine after intravenous, intraperitoneal and oral administration to Atlantic halibut (Hippoglossus hippoglossus) held in seawater at 9°C

The pharmacokinetic properties of the antibacterial agent flumequine were studied after intravenous, intraperitoneal and oral administration to Atlantic halibut (Hippoglossus hippoglossus) held in seawater at 9 degrees C and weighing 1.5-2.5 kg. Following intravenous injection the plasma drug concentration-time profile showed three distinct phases. The distribution half life (t(1/2) alpha) was estimated to be 0.8 h and the terminal elimination half life (t(1/2) gamma) to be 43 h. Total body clearance (Cl-T) was determined to be 0.052 l/kg h(-1). The volume of distribution at steady state, V-d(ss), was estimated to be 2.3 l/kg indicating good tissue penetration of flumequine in Atlantic halibut. The peak plasma concentration (C-max) and the time to peak plasma concentrations (T-max) were estimated to be 2.7 and 6.1 mu g/ml and 20 and 10 h, respectively, following oral administration of medicated feed or intraperitoneal injection. The bioavailabilities were calculated to be 31 and 69%, respectively, following oral or intraperitoneal administration. Only traces (< 10 ng/ml) of the metabolite 7-hydroxy-flumequine were found in a few of the plasma samples. Based on a minimum inhibitory concentration (MIC) of 0.0625 mu g/ml for susceptible strains, a single intraperitoneal injection of 25 mg/kg of flumequine maintain plasma levels in excess of 0.25 mu g/ml corresponding to 4 times the MIC-value, for approximately 10 d. The corresponding value for a single oral dose of 25 mg/kg of flumequine given as medicated feed, was 5 d. (C) 1997 Elsevier Science B.V.