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

Chickens were used to investigate plasma disposition of difloxacin after single intravenous (IV) and oral dose (10 mg/kg body weight (SW)) 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(1/2)beta) 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 mu g/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 (10 mg 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 mu g/kg and 136.4 +/- 18.3 and 10.4 +/- 1.2 mu g/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. (C) 2010 Elsevier Ltd. All rights reserved.