Pharmacokinetics Of Robenidine Hydrochloride And Enrofloxacin In Carassius Auratus Gibelio

In recent years,Carassius auratus gibelio has become one of the major freshwater aquaculture species in China.However,large-scale intensive farming has brought serious disease problems,especially the most serious bacterial and parasitic diseases.Myxosporidia can be parasitic in the carp gills,epidermis,throat,intestine,liver and other tissues or organs.It has caused harm to the industry that has brought significant economic losses.Therefore,a drug with a strong insecticidal effect is needed to reduce the occurrence of the disease.More and more serious bacterial resistance problems caused a lot of trouble to the use of antimicrobial drugs.Chlorobenzene guanidine hydrochloride is fishery drugs permitted by National Animal Husbandry and Veterinary Breau,but there is no research on the pharmacokinetics of chlorphenoguanidine hydrochloride in Carassius auratus gibelio.Aiming at the present situation of crucian carp culture in China,this paper firstly established the method of detecting chlorobenzidine hydrochloride in different tissues of Carassius auratus gibelio,then studied the pharmacokinetics of chlorphenoguanidine hydrochloride in Carassius auratus gibelio through oral administration via drug-medicated feed to determine its distribution and elimination in different tissues of Carassius auratus gibelio.According to the law to eliminate edible muscle tissues combined with the highest residue limit criteria of relevant countries and organizations,to determine the drug withdrawal period about the chlorphenylguanidine hydrochloride in the body of Carassius auratus gibelio,to provide a scientific basis for the rational use of chlorphenylguanidine hydrochloride in fish production.1.RP-HPLC method for determination of robenidine hydrochloride residue in Carassius auratus gibelioBased on the comparation of the effects of different flows on the chromatographic behavior of chlorophenyl guanidine hydrochloride and the effects of different extraction methods of recovery chlorophenyl guanidine hydrochloride,we established a RP-HPLC method for the determination of chlorphenoguanidine hydrochloride in different tissues such as plasma,intestines,kidney,gallbladder,hepatopancreas,throat,gill,brain and muscle.of Carassius auratus gibelio.The mobile phase was acetonitrile and 0.01 mol/L methanoic acid.Aglient Zorbax SB-C18(4.6×150mm,5?m)was used with a mobile phase flow rate of 1.0 mL/min and column temperature of 30?.Ultraviolet detection was used with wavelength of 317 nm.Sampling volume was of 10 ?L.The method was found to be linear and reproducible in the concentration ranges of 0.01~10 ?g·mL-1 with the correlation coefficient of 0.9998.Robenidine hydrochloride in Carassius auratus gibelio were extracted by acetonitrile,and the average recoveries of sulfadiazine and trimethoprim from plasma,intestines,kidney,gallbladder,hepatopancreas,throat,gill,brain and muscle were 80.06%~102.02%,respectively.The relative standard deviations for intra-day and inter-day precisions of Robenidine hydrochloride were 2.16%~7.41%,respectively.The quantitative detection limits of Robenidine hydrochloride was 0.0 ?g/m L,respectively.The method is simple,reproducible and suitable to determine Robenidine hydrochloride in Carassius auratus gibelio.2.Pharmacokinetics of Robenidine hydrochloride in Carassius auratus gibelio.The pharmacokinetics,distribution and elimination of robenidine hydrochloride in silver crucian carp,Carassius auratus gibeliowere were investigated after oral administration at 20 mg·kg-1 body weight via medicated feed at the water temperature of(25±1)?.ROBH concentrations in plasma and tissues were determined by HPLC method.The results showed that the plasma ROBH concentration-time of silver crucian carp could be best described by a two-compartment model with first-order absorption.The peak time(Tmax)was 4h,and the maximum concentration(Cmax)was 1.117 mg·L-1,the area under the concentration-time curve(AUC0-?)was 68.39 mg·L-1·h,and the elimination hal-life(t1/2?)of plasma was 56.86 h.ROBH has a wide distribution in tissues of Carassius auratus gibelio.ROBH concentration,Cmax in tissues in sequence from high to low was intestines,kidney,hepatopancreas,gallbladder,gill,throat,brain and muscle;AUC0-? in tissues in sequence from high to low was intestines,kidney,gallbladder,hepatopancreas,throat,gill,brain and muscle.After ROBH-medicated feed were fed by silver crucian carp,robenidine hydrochloride was absorbed by intestine and entered into hepatopancreas,distributed to various tissues and organs via blood circulation,and then excreted mainly by the kidneys,which was confirmed by the larger Vd value.It was observed that ROBH could distributed into throat,gill and brain,which myxosporidia could infect.If the maximum residue limits(MRL)in muscle is 10 ?g·kg-1,the withdraw period should not be less than 15 days under this experimental condition.3.Clinical application of enrofloxacin and pharmacokinetic evaluationIn this study,we conducted sampling analysis in-depth production.Experimental ponds is located in Yancheng City,Jiangsu Province,Sheyang salt field large-scale breeding area of carp.In this study,drug ponds with bacterial disease were selected and administered in accordance with local medication practices to obtain more realistic and reliable data to facilitate the actual production of drug analysis and guidance.The sampling method was collected samples before and after multiple administrations to obtain the general metabolic profile of the drug in the animal and the highest possible drug concentration in the plasma.The results showed that the highest plasma concentration of enrofloxacin in Carassius auratus gibelio was 1.130?g·mL-1 and the highest concentration of ciprofloxacin is 0.026?g·mL-1,enrofloxacin and its metabolite ciprofloxacin in the Carassius auratus gibelio to eliminate slower,longer retention time.The obtained experimental data show that the dosage of Pond is small,The highest drug concentration is only about 1.130?g·mL-1.Faced with an increasingly serious problem of bacterial resistance,it is difficult to achieve a good therapeutic effect.Therefore,in the actual clinical medication,we have to take into account a variety of factors such as the severity of the disease,the feeding of sick fish and the previous medication records,etc.,to ensure a good therapeutic effect and reduce the occurrence of drug resistance.