Study Of Praziquantel Metabolism In Grass Carp (Ctenopharyngodon Idella) And Crucian (Carassius Auratus) And Salinity Effect On Metabolism

With the continuous improvement of Chinese intensive aquaculture, the high density farming model was continuous development. Aquatic animals will reduced resistance to pathogenic microorganisms living in the environment with the poor living environment,large population density and poor feed quality. So aquatic animal diseases occur more and more frequently especially the Parasitic diseases. Parasitic disease not only brings great economic loss to the farmers, but also has a great impact on the development of aquaculture. The drugs using is a common and effective means to prevent and control parasitic diseases. In order to protect the safety of aquatic products and people’s health, the state issued a series of standards and regulations to control the use of fishing drugs strictly. Praziquantel is a new broad-spectrum anti and effective parasite drug. The PZQ Powder preparation with the appropriate matrix which Has the advantages of high biological safety, good palatability, high solubility, good absorption is widely use In aquaculture. Grass carp(Ctenopharyngodon idellus) is an economically important species of farmed fish. In China, grass carp has a widespread breeding distribution scope, covering different salinity areas in the eastern and northwestern regions, and freshwater areas of the central and southern regions. Considering that grass carp are cultured in both freshwater and brackish water, it is necessary to investigate possible tissue distribution and praziquantel elimination differences in grass carp under different water environments. We believe that this study would help better formulate effective PZQ regimens in treating monogenean infections of fish.The main research of this paper and the results are as follows:(1)The grass carps were randomly divided into two groups: freshwater group and brackish water group. The fish were given 10 mg/kg of the PZQ solution via gavage using a stomach tube and then study the differences in grass carp Pharmacokinetic between the two experimental groups. The results showed that the salinity had a significant effect on the drug concentration of plasma(p < 0.01), musle(p < 0.01), liver(p < 0.01) and kidney(p < 0.01) in the all sampling time points between the brackish water grass carps and the freshwater grass carps. In most sampling time points, the plasma and tissue PZQ levels in brackish water grass carps were lower than that in the freshwater grass carps. These findings indicated that PZQ elimination in brackish water grass carps was more rapid than that in freshwater grass carps.(2) The grass carps were randomly divided into two groups: freshwater group and brackish water group. The fish were given 500 mg/kg of the PZQ premix solution via gavage using a stomach tube and then study the differences in grass carp pharmacokinetic between the two experimental groups. The results showed that the salinity had a highly significant effect on all of the plasma musle, liver and kidney between the brackish water and the freshwater grass carps(p<0.01). In most sampling time points, the effective components of PZQ premix in plasma and tissue in brackish water grass carps were lower than that in the freshwater grass carps. The elimination half-lives(t1/2β) in all the tissues and plasma of freshwater grass carp were longer than that in brackish water grass carp. These findings indicate that the osmotic pressure in the water environment may affect the tissue absorption and elimination of praziquantel premix in grass carp, which suggested the dosing strategy of praziquantel premix should be adjusted by the water environment.(3) With praziquantel and 4-hydroxy naphthenic acid methyl ester as the raw material,we synthesis the maximum content in the people and animals after PZQ metabolism. The NMR analysis result of the synthetic product tell us although it has small amount of impurity the target product reach 95%. The result of high performance liquid chromatography showed tha the purity was 96.5%.The synthesis process of this method is simple and the metabolites of praziquantel in high purity.(4) The crucian(Carassius auratus) were given 10 mg/kg of the PZQ solution via gavage using a stomach tube and then measure the concerntrations of PZQ and its metabolite M1 in plasma and tissues in order to study the pharmacokinetic and metabolism in crucian. The results showed that PZQ concentration-time profiles in plasma and tissues were best described by a second-compartmental open pharmacokinetic model. The peak time of Praziquantel metabolite(M1) concerntrations almost all delay. Due to the liver residue of Praziquantel and its metabolites was highest and liver elimination was slowest, we preliminary inference the fish liver is the drug residual target tissue. Praziquantel metabolite(M1) concerntrations has a high proportion of total residue indicated that praziquantel prototype may not be the marker residue in crucian.