Pharmacokinetics, tissue distribution, and metabolism of flumequine in channel catfish ( Ictalurus punctatus)

Abstract

The pharmacokinetics and metabolism of the fluoroquinolone drug flumequine (FLU) were examined after intravascular (1 mg/kg) or oral (5 mg/kg) dosing in channel catfish. Parent FLU concentrations in plasma declined slowly after intravascular dosing, with a half-life of 25 h. After oral dosing, FLU concentrations in plasma were highest (3.1 μg/ml) at 14 h after dosing; absorption and elimination half-lives were 4.9 and 22 h, respectively. The oral bioavailability of FLU was 44%, based on normalized plasma data. Plasma protein binding of parent FLU was extensive, but saturable (88%–55% bound at 0.125–8.0 μg/ml). After oral dosing with 14C-labeled FLU, radioactive residues were evenly distributed among the major tissues analyzed, with peak concentrations occurring at 12–24 h. Residue concentrations were highest in liver (6.2 μg/g) and lowest in muscle (1.8 μg/g) at 24 h. Only parent FLU was found in muscle and was eliminated with a half-life of 26 h. FLU and its metabolites were recovered in urine and bile. Residues in bile consisted almost entirely of a taurine conjugate of FLU. In urine, the taurine conjugate and hydroxy-FLU metabolites were found, in addition to the parent compound.