| Fish farming is now an important industry in China. However, fish disease is becoming a serious problem. Various antimicrobial drugs are used extensively to control fish diseases. Fluoroquinolones have been recently introduced as effective antibacterial agents in fish farming, such as flumequine, sarafloxacin, enrofloxacin et al. Difloxacin is a broad-spectrum antibacterial chemical agent of the fluoroquinolone family used only for animals, however, few pharmacokinetic and residue studies have been conducted with DIF in fish farming.The HPLC system used was the Agilent 1100 series equipment, with an automatic injection performed on a ZORBAX SB-C18, 5μm (150×4.6mm2) stainless steel column with a guard column (12.5×4.6mm2), which was programmed to inject a sample of 20μL. Thermostatted Column Compartment was used to maintain the column temperature at 45℃. Detection of difloxacin was performed on the variable wavelength detector at 280nm. The mobile phase consisted of a phosphate buffer (0.01M)-acetonitrile (80/20 v/v) solution (pH=3), and the flow rate was 0.8mL/min.The plasma drug concentration-time data were fitted using a single-compartment model and a two-compartment model at 10℃ and 20℃, respectively. The absorption rate constant (Ka) of DIF was found to be 0.85 and 1.27 h-1 at 10℃ and 20℃, respectively, whereas the elimination half-life (t1/2β) of the drug was 95.36 h at 10℃ and 48.93 h at 20℃. The area under the serum concentration-time curve (AUC) was 1361.79μg·mL-1·h at 10℃ and 355.19 μg·mL-1·h at 20℃. The distribution volume (Vd/F) of DIF was computed as 2.02 and 4.02 L·kg-1 at 10℃ and 20℃, respectively. The total clearance of DIF (CLb) was estimated to be 0.015 and 0.056 L·h-1·kg-1 at 10℃ and 20℃, respectively. The time-point of maximum plasma concentration of the drug (Tp) and the maximum plasma concentration (Cmax) were calculated as 5.65 h and 9.49μg/mL at 10℃ and 2.21 h and 10.28μg/mL at 20℃. the tissue residue study was conducted after repeated oral administration at a dosage of 20 mg/kg b.w. for 3 times. DIF can be detected in the muscle, liver, kidney, and skin at the 15th day after the last administration. The elimination half-life of DIF in skin is longest than that in other tissues at 10℃. The concentration of DIF in skin was detected highest in skin after 15 days at 20℃.The study of pharmacokinetics at two water temperatures revealed that a single dose of 20mg/kg b.w. after oral administration might be sufficient for the long-term maintenance of therapeutic concentration in the plasma of DIF, regardless of the water temperature. Based on the results of the residue study, to ensure tissues samples are safe for consumption, it is suggested that the withdrawal periods should not be less than 64 and 18 days at 10℃ and 20℃, respectively.
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