Pharmacokinetics, tissue distribution, and depletion of enrofloxacin and its metabolite ciprofloxacin in the northern snakehead (Channa argus) following multiple oral administration

Abstract Enrofloxacin (ENR) is effective in the prevention and treatment of bacterial infections caused by various fish pathogenic bacteria such as Aeromonas spp., Vibrio spp., Nocardia and Yersinia spp. The purpose of this work was to explore the pharmacokinetics (PK), tissue distribution, and depletion of ENR and its main metabolite, ciprofloxacin (CIP), in northern snakehead (Channa argus) reared at 25 °C during and after repeated oral dose of 10 mg/kg animal body weight per day for a total of 5 days. ENR and CIP concentrations were simultaneously determined in the plasma, liver, kidney, gill, and muscle with adhering skin by HPLC with fluorescence detection. Using a non-compartmental analysis, PK parameters were derived from the mean concentration versus time data of ENR and CIP. The results showed a slow absorption, long half-life and wide tissue distribution of ENR in the northern snakehead. The maximum concentrations of ENR in the plasma, muscle plus skin, liver, kidney, and gill tissues were observed at 3, 6, 6, 6, and 9 h post treatment, respectively, and the corresponding depletion half-lives (T1/2z) were 78.00, 83.24, 82.56, 126.07, and 68.70 h, respectively. The extent of ENR distribution into the tissues followed the decreasing order of liver > kidney > gill > plasma > muscle plus skin. The highest concentrations of both ENR and CIP were observed in the liver, suggesting that liver is the major site of ENR metabolism in northern snakehead. The Cmax/MIC and AUC24/MIC ratios obtained in the present study indicated that the ENR regimen employed would be effective in treatment of infections caused by susceptible strains with MIC values below 0.7 μg/mL. Based on the calculation results, a reasonable withdrawal period should not be less than 18 days at 25 °C for ENR in northern snakehead after treatment ceased.