PHARMACOKINETICS AND BIOAVAILABILITY OF FLUMEQUINE AND OXOLINIC ACID AFTER VARIOUS ROUTES OF ADMINISTRATION TO ATLANTIC SALMON IN SEAWATER

The present preclinical study was performed to investigate the pharmacokinetics of flumequine in Atlantic salmon (Salmo salar L.) in seawater after administration of different doses and dosage formulations. Flumequine was administered intravenously (dose 4.9 mg/kg fish) and orally from the drug delivery system Aqualets as Apoquin 5 g/kg (dose 25 mg/kg) and 10 g//kg (dose 50 mg/kg), respectively. Experiments were carried out with oxolinic acid administered in the same way for the purpose of comparing the two compounds. The seawater temperature was 5 +/- 0.2-degrees-C in all experiments. The pharmacokinetic calculations showed that the distribution half-life for flumequine was t1/2alpha = 1.3 h and for oxolinic acid t1/2alpha = 0.7 h. The drugs were absorbed rapidly, and flumequine reached a plasma concentration of C(max) = 2.26 mug/ml after a single oral dose of 25 mg/kg, whereas oxolinic acid reached C(max) = 0.99 mug/ml. The apparent bioavailability of flumequine was found to be 40-45%, whereas the apparent bioavailability of oxolinic acid varied from 25% at a dose of 50 mg to 40% at a dose of 25 mg/kg body weight of fish. The distribution profile of flumequine in the various compartments of fish appeared to be different from that of oxolinic acid. After a single oral dose (25 mg/kg) the areas under the concentration-time curves showed that flumequine was 2.3 times more concentrated in plasma and 2.6 times more concentrated in liver compared to oxolinic acid. In muscle the difference was less pronounced, flumequine being 1.4 times more concentrated than oxolinic acid.