| Sulfadimidine, Sulfamethoxydiazine and Sulfadiazine are commonSulfonamides extensively used in aquaculture. Cytochrome P450family (CYP450) is one of the main enzymes involved in drug metabolism in biology. Asone of important members in CYP450family, CYP2C plays an important rolein the process of Sulfonamides drug metabolism in Fenneropenaeus chinensis.The purpose of this study is to obtain the metabolic rule of Sulfonamides in F.chinensis by comparing the characteristic of pharmacokinetics in three kinds ofSulfonamides. In order to provide theoretical basis for clinical drug rationallyin shrimp, the relationship between drug metabolism and CYP2C expressionwere also explored in this paper. The research was divided into three part.The pharmacokinetics of Sulfadimidine (SM2), Sulfamethoxydiazine(SMD) and Sulfadiazine (SD) in F. chinensis by using the high performanceliquid chromatography (HPLC). The study was performed at (24.6±2.4)℃. Allthe health shrimp received oral administration at a level of100mg·kg-1. Theresults showed that the hemolymph concentration–time course of SM2,SMDand SD can be described by a two-compartment open model with the first orderabsorption after oral administration. The main pharmacokinetic parameters ofSM2including T1/2β, AUC(0—72), Vd, CL, Tmaxand Cmaxwere25.812h,34.066mg·L-1·h-1,94.553L·kg-1,2.608L·h-1·kg-1,2h,1.07mg·L-1, respectively; Themain pharmacokinetic parameters of SD including T1/2β, AUC(0—72), Vd, CL,Tmaxand Cmaxwere46.446h,45.39mg·L-1·h-1,97.207L·kg-1,1.504L·h-1·kg-1,1h,1.17mg·L-1, respectively; The main pharmacokinetic parameters of SMDincluding T1/2β, AUC(0—72), Vd, CL, Tmaxand Cmaxwere66.296h,65.917mg·L-1·h-1,40.015L·kg-1,0.763L·h-1·kg-1,2h,2.00mg·L-1, respectively; Insummary, SMD was more widely distributed than SM2and SD. SM2have theshortest elimination half-life, followed by SD, The elimination half-life of SMDwas the longest.In this study, the pharmacokinetics of Sulfamethazine (SM2),Sulfamethoxydiazine(SMD) and Sulfadiazine(SD) in gill, hepatopancreas and muscleof Fenneropenaeus chinensis were investigated following oral administration (100mg·kg-1) at (24.6±2.4). The results showed that for SM2, the values of T1/2βin gill,hepatopancreas and muscle were23.067,34.162and16.559h, respectively. For SD,the values of T1/2βin gill, hepatopancreas and muscle were29.157,34.272and27.929h, respectively. For SMD, the values of T1/2βin gill, hepatopancreas and muscle were 47.657,55.271and32.237h, respectively. The rate of different pharmic eliminationin the same tissue was in the following order: SM2>SD> SMD. The rate of pharmicelimination in different tissues by oral same administration was in the following order:muscle> gill> hepatopancreas. For SM2, the values of CL in gill, hepatopancreas andmuscle were0.673,0.171and0.464L·h-1·kg-1, respectively. For SD, the values of CLin gill, hepatopancreas and muscle were0.496,0.214and0.463L·h-1·kg-1,respectively. For SMD, the values of CL in gill, hepatopancreas and muscle were0.29,0.082and0.362L·h-1·kg-1, respectively. Therefore, the slowest clearance rate in thesame tissue were SD. For the same pharmacokinetics, the fastest clearance rate wasin the gill. For SM2, the values of AUC(0—72)in gill, hepatopancreas and muscle were138.476,493.02and206.572mg·L-1·h-1, respectively. For SD, the values of AUC(0—72)in gill, hepatopancreas and muscle were147.919,379.039and186.495mg·L-1·h-1,respectively. For SMD, the values of AUC(0—72)in gill, hepatopancreas and musclewere218.024、629.311、229.819mg·L-1·h-1, respectively. The AUC was highest inhepatopancreas for the same oral administration, the highest values of AUC was inhepatopancreas for the same pharmacokinetics. The results illustrated the metaboliclaw of the three sulfa drugs in gill, hepatopancreas and muscle of F. chinensis, andindicated that hepatopancreas was the main tissue of F. chinensis for sulfa drugsresidue within72h.The part sequence of CYP2C was cloned in F. chinensis by the techniques ofRT-PCR and RACE. Analysis of nucleotide sequence revealed that the CYP2C cDNAbelonged to the CYP450super family. RT-PCR analysis showed that constitutivelyexpressed in the tissues of haemolymph, hepatopancreas, gill, muscle, stomach, crustand intestine at different expression levels. The level in hepatopancreas appeared to begreater than in the other tested tissues. The expression of CYP2C in haemolymph wasthe least level. The rapid and dynamic expression profiles in hepatopancreas of F.chinensis feeded with Sulfadimidine, Sulfamethoxydiazine and Sulfadiazine weretested. The results showed that the CYP2C expression profiles of Sulfadimidine andSulfamethoxydiazine were in accordance with the changing concentration trend ofthese two drugs in hepatopancreas. In the situation of the same drug concentration, theexpression of CYP2C in the group of Sulfadimidine was much higher thanSulfamethoxydiazine. |
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