Pharmacokinetic Of Compound Sulfadiazinein GIFT

Sulfadiazine is one of sulfa drugs which is commonly used in aquaculture, the advantage of Sulfadiazine is antimicrobial resistance, lower protein-binding, easy to enter the organization. But in recent years, the resistance of sulfadiazine is gradually increases.The use of sulfonamides has increased over time especially in combination with trimethoprim.Sulfonamides and trimethoprim are bacteriostatic agents when each drug used individually, whereas they exert a bactericidal effect when used in combination, and thus results in a synergistic action In medical practice,a combination of sulphadiazine and trimethoprim are antibacterial compounds frequently used in aquaculture to treat bacterial disease, such as:vertical scales, vibriosis, gill disease and so on. Drug is Irrationally used not to guarantee the therapeutic effect of drugs,caused damage of liver, kidney and other organ damage, pollute the environment of aquaculture and cause food safety problems;.So It is very necessary to study pharmacokinetic of compound sulfadiazine in vivo of tilapia. The concentration of SD and TMP in the plasma and muscles of the fish were determined by high performance liquid chromatography(HPLC). To study pharmacokinetics of SD and TMP in vivo of tilapia at temperature of28.In addition, to found the internal rules of the temperature effect on drug and the pharmacokinetics processes of Sulfadiazine(SD) and Trimethoprim(TMP) in vivo of tilapia.It will provide scientific basis for aquatic medication. The main findings of the study are as follows.1.The pharmacokinetic of compound sulfadiazine in vivo of tilapiaPharmacokinetics of sulfadiazine (SD) in tilapia were researched by HPLC method after food feeding tilapia120mg/kg of SD and TMP at28±2temperature. Results showed the Cmax were22.48、14.238、25.038/52、9.39/6.6ug/mL (ug/g), the Tmax were10.55,922,2.0/8.0、(Tmaxl/T ax2)and4.0/10h(Tmaxl/Tmax2) in blood,muscle,liver and kidney of tilapia. Bimodal phenomenon of concentration-time curve were found in liver and kidney,suggesting that there were Non-homogeneous absorption phenomenon in the Gastrointestinal tract of tilapia and the absorption in the back section was less than the front section. Cmax of SD in the liver was highest in all the tissues while eliminated rapidly after the peak concention suggesting that first-pass elimination were occured in the liver of tilapia.Trimethoprim had similar conclusions with sulfadiazine. Results showed the Cmax of TMP were2.4、7.13、15.53、20.46/10.46ug/mL (ug/g); the Tmax were6.04,11.03、4.0、4.0/24.0h,(Tmaxl/Tmax2); in blood,muscle,liver and kidney of tilapia.The Cmax of TMP is in the kidney, the reason is that trimethoprim is hydrophilic,as sulfadiazine is lipophilic.2.Pharmacokinetic of Compound Sulfadiazine in the Blood of GIFT at Different TemperatureTO investigate the pharmacokinetic characteristics and changes of Sulfadiazine(SD) and Trimethoprim(TMP) in the blood of GIFT Nile tilapia at different temperatures.Compound Sulfadiazine which contain two composition of Sulfadiazine and Trimethoprim were chosen by orally administered in single dose of120mg/kg to GIFT Nile tilapia at18℃,23℃,28℃and33℃.The concentration of Sulfadiazine and Trimethoprim in plasma of Tilapia was determined by HPLC method. Results showed that Cmax of Sulfadiazine were12.4μg/ml,19.6μg/ml,22.48μg/mL and30.05μg/mL at18℃,23℃,28℃and33℃, the Cmax of Trimethoprim were1.22μg/mL,2.065μg/mL,2.44μg/mL and2.7μg/mL respectively, there were higher peak plasma concentration (Cmax) with the higher temperature.The elimination(T1/2ke) of Sulfadiazine were18.22h,17.89h,16.9h and12.99hat18℃,23℃,28℃and33℃,T1/2ke of trimethoprim were16.391h、7.081h、5.99h and4.04h. respectively, there were faster elimination of trimethoprim and sulfadiazine with the higher temperature in GIFT Nile tilapia. Concentration ratio of sulfadiazine/trimethoprim were9.57:1-11.01:1,6.30:1-8.40:1,5.4:1-9.15:1,4.2:1-20.6:1within10h after administration,which were all at the suggest synergistic activity ratios ranging of1:1-40:1. The results showed that the temperature could affect the absorption and elimination of the drugs in GIFT Nile tilapia significantly,could improve the maximum plasma concentration and quicken the elimination of the drugs, but had little effect to the ratio of compound sulfadiazine.