Pharmacokinetics and tissue residues of difloxacin in crucian carp ( Carassius auratus) after oral administration

Abstract

The study was conducted to evaluate the pharmacokinetic disposition of difloxacin (DIF) with a single dose of 20 mg/kg body weight after oral administration in crucian carp ( Carassius auratus, 250 ± 30 g) at water temperatures of 10 °C and 20 °C. DIF concentration in plasma and tissues was determined using high-performance liquid chromatography (HPLC). The plasma drug concentration–time data were fitted using a single-compartment model and a two-compartment model at 10 °C and 20 °C, respectively. The absorption rate constant ( K a) of DIF was found to be 0.85 and 1.27 h − 1 at 10 °C and 20 °C, respectively, whereas the elimination half-life ( t 1/2 β ) of the drug was 95.36 h at 10 °C and 48.93 h at 20 °C. The area under the serum concentration–time curve (AUC) was 1361.79 μg ml − 1 h at 10 °C and 355.19 μg ml − 1 h at 20 °C. The distribution volume ( V d/ F) of DIF was computed as 2.02 and 4.02 l kg − 1 at 10 °C and 20 °C, respectively. The total clearance of DIF (CL b) was estimated to be 0.015 and 0.056 l h − 1 kg − 1 at 10 °C and 20 °C, respectively. The time-point of maximum plasma concentration of the drug ( T p) and the maximum plasma concentration ( C max) were calculated as 5.65 h and 9.49 μg/ml at 10 °C and 2.21 h and 10.28 μg/ml at 20 °C. After repeated oral administration at a dosage of 20 mg/kg body weight, DIF was detected in the muscle, liver, kidney, and skin for 15 days after the last administration. The results revealed that the depletion of DIF in the crucian carp becomes slower with a long half-life time, especially at lower water temperature.