Plasma disposition and tissue depletion of difloxacin and its metabolite sarafloxacin in the food producing animals, chickens for fattening.

Arturo Anadón, Frank H Suárez, María A Martínez, Víctor Castellano, Marta Martínez, Irma Ares, Eva Ramos, Felipe Gamboa, María R Martínez-Larrañaga

Index: Food Chem. Toxicol. 49(2) , 441-9, (2011)

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Abstract

Chickens were used to investigate plasma disposition of difloxacin after single intravenous (IV) and oral dose (10 mg/kg body weight (BW)) and to study residue depletion of difloxacin and its major metabolite sarafloxacin after multiple oral doses (10 mg difloxacin/kg BW, daily for 5 days). Plasma and tissue samples were analyzed using a HPLC method. After IV and oral administration, plasma drug concentration-time curves were best described by a two-compartment open model. Mean (± SD) elimination half-lives (t(½)β) of difloxacin were 9.53±1.00 and 12.23±1.81 h after IV and oral administration. Maximum plasma concentration was 2.34±0.50 μg/ml and interval from oral administration until maximal concentration was 1.34±0.03 h. Oral bioavailability was found to be 68.89±15.21%. Difloxacin was converted to sarafloxacin. After multiple oral dose (10mg difloxacin/kg BW, daily for 5 days), mean kidney, liver, muscle and skin + fat tissue concentrations of difloxacin and sarafloxacin ranging between 604.8±132.5 and 368.1±52.5 μg/kg and 136.4±18.3 and 10.4±1.2 μg/kg, respectively, were measured 1 day after administration of the final dose of difloxacin. A withdrawal time of 5 days was necessary to ensure that the residues of difloxacin were less than the maximal residue limits (MRL) or tolerance established by the European Union.Copyright © 2010 Elsevier Ltd. All rights reserved.