Oral bioavailability, tissue distribution and depletion of flumequine in the food producing animal, chicken for fattening

Abstract

Chickens were used to investigate kinetic properties including metabolism of flumequine after single IV and oral dose, and to study tissue depletion of flumequine after multiple oral doses. Plasma and tissue (muscle, kidney, liver and skin plus fat) concentrations of flumequine and its metabolite 7-hydroxyflumequine were determined using a HPLC method. After IV and oral administration (single-dose of 12 mg flumequine/kg bw), plasma concentration-time curves were best described by a two-compartment open model. Elimination half-life and mean residence time of flumequine in plasma were 6.91 and 5.90 h, respectively, after IV administration and 10.32 and 8.95 h after oral administration. Maximum plasma concentration was 3.62 microg/ml and interval from oral administration until maximum concentration was 1.43 h. Oral bioavailability was found to be 57%. Flumequine was converted to 7-hydroxyflumequine. After oral administration (24 mg/kg bw every 24 h for 5 days), renal and hepatic concentrations of flumequine (18-25 microg/kg) persisted for 4 days; however, at that time, flumequine residues were not detected in skin plus fat and muscle tissues. Flumequine administered at a dosage of 24 mg/kg bw every 24h for 5 days, with a withdrawal time of 2d ays, resulted in flumequine concentrations in target tissues that were less than the European Union maximal residue limits.