Pharmacokinetics And Residues Of Florfenicol In Blunt-snout Bream

Blunt-snout bream?Megalobrama amblycephala?is an herbivorous freshwater carp of economic importance in China with a worldwide distribution.Florfenicol?FFC?is a broad-spectrum chloromycetin series antibiotics,because its high potency and safety in humans,FFC has been developed exclusively for veterinary medicine and is used extensively in fish farming as a chemotherapeutic agent in China.The concentration of FFC and FFA in M.amblycephala plasma,liver,kidney and muscle were detected by high performance liquid chromatography?HPLC?.The pharmacokinetics and residue study of FFC and FFA were conducted by this method in health M.amblycephala at 18?C and 28?C two water temperature with a single oral administration.1.A simple and rapid method for the simultaneous extraction and determination of FF and FFA in plasma,liver,kidney and muscle of blunt-snout bream by HPLC is described.The analyses were performed on an Agilent LC1200?Agilent,USA?with a UV detector set to 225 nm.Analyte separation was achieved on a reverse phase column from Shodex C18-120-5 4E reverse-phase column?250×4.6 mm i.d.,5?m?.The mobile phase was acetonitrile and phosphate buffer?32?68,V/V?.The column temperature was set to 42?,and the flow rate was 1.0 mL/min.Acetone and n-hexane were used as extraction and defatted solvent,respectively.The results showed that the HPLC analysis of FF and FFA was rapidly performed with a high degree of reproducibility.A linear relationship existed in the calibration curve over the range of 0.05²5.00?g/mL,with a correlation coefficient?r?typically greater than0.999.The percentage relative standard deviations for inter-day and intra-day precisions were 2.68⁴.61%and 3.07⁵.09%,respectively.The FFC and FFA recovery rates were 86.29¹04.63%and 85.42¹01.68%,respectively.The LODs were 0.01–0.09?g/g for FF and FFA in plasma and tissues.2.The pharmacokinetics of FF and FFA were studied in blunt-snout bream after a single oral administration at 18?C and 28?C two water temperature.And the pharmacokinetics of FFC and FFA after fed with fodder which mixed with FFC in M.amblycephala also been conducted at 28?.As a result a no-compartment model was developed to describe the pharmacokinetics of FFC in M.amblycephala.All tissues in blunt-snout bream displayed obvious double peaks.In oral group,the maximum plasma concentration(C_max)and the time to reach C_max(T_max)of FFC were calculated as 5.89?g/mL and 5.97 h at 18?,respectively,versus a Cmax of 6.21?g/mL and a Tmax of 2.84 h at 28?.The elimination half-life?t1/2k??was 26.75 h at 18? and16.14 h at 28?.The total body clearance?CL?of FFC was calculated as 0.09 and0.15 L/kg/h at 18? and 28?,respectively.The areas under the concentration–time curves?AUCs?were 265.87?g·h/mL at 18? and 163.31?g·h/mL at 28?.Compared to the 28? group,the absorption rate in the 18? group was significantly decreased,T_maxax was delayed,C_maxax was reduced,total clearance?CL?was decreased,the elimination half-life(t_1/2k?)was extended,and the area under the curve?AUC?was increased.These results reveal that the depletion of FFC and FFA in blunt-snout bream was slower?longer half-life?at the lower water temperature.After multiple administrations for 5 consecutive days of 25mg/kg,the the maximum plasma concentration(C_max)and time to reach FFC peak concentration(T_max)in plasma,liver,kidney and muscle were 4.57?g/mL,2.46?g/g,4.44?g/g and 5h,5h,4h,respectively.The order of t_1/2?was liver?28.41h?>muscle?24.18h?>plasma?17.90h?.All the data of medical-fed group were lower than that of oral group.3.In the residue elimination study with a dose of 25 mg/kg body weight for 3continuous days at 28?.Considering a maximum residue limit?MRL?of 1.0 mg/kg for the concentration of florfenicol amine in muscle,the withdrawal period was 10 d?water temperature 28??.