Pharmacokinetics, tissue distribution, and metabolism of flumequine in channel catfish ž / Ictalurus punctatus
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چکیده
Ž . The pharmacokinetics and metabolism of the fluoroquinolone drug flumequine FLU were Ž . Ž . examined after intravascular 1 mgrkg or oral 5 mgrkg dosing in channel catfish. Parent FLU concentrations in plasma declined slowly after intravascular dosing, with a half-life of 25 h. After Ž . oral dosing, FLU concentrations in plasma were highest 3.1 mgrml 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 Ž . 14 extensive, but saturable 88%–55% bound at 0.125–8.0 mgrml . After oral dosing with C-labeled FLU, radioactive residues were evenly distributed among the major tissues analyzed, with peak Ž . concentrations occurring at 12–24 h. Residue concentrations were highest in liver 6.2 mgrg and Ž . lowest in muscle 1.8 mgrg 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. Published by Elsevier Science B.V.
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