Studies On The Pharmacokinetics And Residual Elimination Of Praziquantel In Prech

Intensive and high-density farming conditions lead to occurrence of aquatic animal diseases frequently,especially the parasitic.Praziquantel as a broad-spectrum anti-parasitic drug,was widely used in aquaculture.At the current stage of C hina,irregular use of fishery drugs seriously resulted in drug residues in the fish,which would not only restrict the healthy development of aquaculture,but also threat human health through the food chain.Thus,in this study,perches were taken as testing animals to study the pharmacokinetics and residual elimination regularity of praziquantel.This study provides theoretical basis for the clinical usage of medication,determination of the residual markers,establishment of withdrawal time and the maximum residue limit.A high performance liquid chromatography method with ultraviolet detection for the determination of praziquantel and its 4-hydroxyl metabolites in plasma and fish meat was developed.The flow rate was kept constantly at 1 mL/min with acetonitrile and water as mobile phases.The target drugs were separated by Elite C18(250 mm × 4.6 mm id,5 μm)column with gradient elution,ultraviolet detection at 210 nm,and Diazepam as internal standard quantitative.The results showed that the calibration curves of praziquantel and its 4-hydroxyl metabolites were good linear with the correlation coefficients more than 0.99.The limits of detection and quantification ranged from 0.02 to 0.05 μg/L and 0.05 to 0.1 μg/mL,respectively.Average recoveries were in the range of 68.0% to 91.9% with the intra-day and inter-day coefficient variances less than 9.7%.The perches were given 10 mg/kg of the praziquantel solution via gavage using a stomach tube and then concentration-time data was analyzed by pharmacokinetic program WinNonlin5.2.1 according to a non-compartment model.After the rapidly absorption of Praziquantel in the perch,its peak time in plasma concentration was 1 h and highest plasma concentration was 1.55 μg/mL.The elimination half-life and average residence time were 9.24 h and 11.35 h,respectively.The apparent distribution volume was 6.81 L/kg and the overall elimination rate was 0.51 L?h/kg.The peak time of trans-4-hydroxypraziquantel and cis-4-hydroxypraziquantel were 24 h and 12 h with the peak plasma concentration of 0.26±0.08 μg/mL and 0.11±0.05 μg/mL,respectively.The peak plasma concentrations of metabolites were lower than that of the prototype drug,and the peak time was later than the prototype.The perches were bathed at a concentration of 1.5 mg/L for 12 h and then raw data was analysed by WT1.4 program.And considering the residue in other edible tissues such as perch skin,under the experimental conditions,it is recommended to set the MRL to 0.02 μg/g when the muscle as the target tissue,the praziquantel as the residual marker and withdrawal time not less than 5 d.When the trans-4-hydroxypyrazolone as the residual marker and the withdrawal time was not less than 6 d.And further speculation was that the praziquantel prototype may not be the residual marker of praziquantel in the perch.