Pharmacokinetics And Residue Elimination Of Enrofloxacin And Its Metabolite In Yellow Catfish (Pelteobagrus Fulvidraco) At Different Temperatures

Enrofloxacin is a broad-spectrum,efficient and low toxicity antibacterial drug,which can prevent and treat bacterial pathogen infection of aquatic animals.It is widely used in the aquaculture of yellow catfish（Pelteobagrus fulvidraco）.However,fishermen lack scientific guidance in the administration,and only rely on experience,resulting in the decline of efficacy and excessive residue of drug.In addition,aquatic animals are ectothermic animals,and the temperature of water is an important factor affecting efficacy and metabolism.It is essential to clarify the pharmacokinetic and residual elimination of drug in aquatic animals at different temperatures for guiding scientific medication and ensuring the safety of aquatic products.Therefore,this study discussed the pharmacokinetics and residue elimination of enrofloxacin and metabolite（ciprofloxacin）in yellow catfish at different temperatures,so as to provide theoretical basis for administer in aquaculture.The plasma,muscle plus skin,gill,liver and kidney of yellow catfish were collected at 0.17,0.25,0.5,1,2,4,6,8,12,24,48,72,96,and 120 h after a single oral dose of 20 mg/kg B.W.at 20,25,and 30℃.The concentrations of enrofloxacin and ciprofloxacin were determined by high-performance liquid chromatography fluorescence after sample processing.The pharmacokinetic parameters of the two compounds were calculated by the 3P97 software based on a non-compartmental model.The pharmacokinetic parameters were compared at different temperatures.The results showed that the terminal elimination half-life(T_1/2?z)of enrofloxacin in plasma and tissues were decreased from 52.93,61.20,51.34,51.61,56.85 h to 16.62,23.86,14.28,16.24,19.57 h with the increased temperature from 20℃to 25℃.However,the T_1/2?zof enrofloxacin in plasma and tissues were increased to 82.06,110.86,29.04,28.47,61.00 h as the increase of temperature from 25℃to 30℃.The peak concentrations(C_max)of enrofloxacin were 2.71,3.23,and 2.43μg/m L appearing at 6,6,and 4 h at 20,25,and 30℃,respectively.The apparent metabolic rates of enrofloxacin in yellow catfish were 25.74%-54.29%,37.10%-53.25%and 22.62%-53.40%at three temperatures,respectively.These results demonstrated that enrofloxacin and ciprofloxacin in yellow catfish were metabolized rapidly and widely distributed.The increase of temperature will accelerate the systemic total body clearance（CL＿F）of the two compounds,and significantly affect other important pharmacokinetic parameters,such as T_1/2λz,C_max,the time to reach the peak concentration(T_max),the area under concentration–time curve(AUC_last).It is generally believed that only free drugs can exert efficacy.The free or unbound concentration of drug can be calculated by the plasma protein binding,and is conducive to formulating a more effective therapeutic regimen.Therefore,this study was to determine the plasma protein binding of enrofloxacin and ciprofloxacin in the plasma of yellow catfish at different concentrations（1,5,and 10μg/m L）with different temperatures（15,20,and 25℃）.Results showed that the lowest plasma protein binding of enrofloxacin and ciprofloxacin were 9.66±4.09%,13.52±4.74%,4.36±0.58%and 4.39±1.03%,2.14±0.36%,13.36±0.96%at 15,20,and 25℃,respectively.The lowest plasma protein binding of enrofloxacin and ciprofloxacin were 37.71±3.71%,17.29±0.69%,4.36±0.58%and 24.22±0.91%,2.14±0.36%,7.04±1.36%at 1,5,and 10μg/m L,respectively.The results revealed that the plasma protein binding of enrofloxacin was decreased as the increase of concentration at the same temperature.The trend of plasma protein binding of ciprofloxacin was decreased first and then increased at same temperature and same concentration.Temperature and concentration significantly affected the plasma protein binding of enrofloxacin and ciprofloxacin.The plasma and tissues of yellow catfish were collected at 1,3,5,7,14,21,28,35,42,49,56,63,and 70 days after daily oral administrations at a dose of 20 mg/kg B.W.for 3 days at 15,20,and 25℃.The samples were processed and determined by the same way as above,and the withdrawal period of enrofloxacin in the plasma and tissues were calculated by WT1.4 software.The results showed that the withdrawal period of enrofloxacin in plasma and tissues were 44,72,66,99,95 days at 15℃,were 32,66,65,86,95 days at 20℃,were 32,61,64,55,59 days at 20℃,respectively.The withdrawal period of enrofloxacin in the plasma and tissues of yellow catfish were decreased as the rise of temperature.Results suggested that the withdrawal period of enrofloxacin is recommended to be 72,66,and 61 days in edible tissues of yellow catfish at 15,20,and 25℃,respectively.