Study Of Pharmacokinetics And Establishment Of Physiological Pharmacokinetic Model (PBPK) Of Sulfadoxine In Flounders

Sulfadoxine (SDM′) is a chemical synthetic and broad-spectrum antimicrobials,which have a very good antibacterial effect on aquaculture fish. Therefore, SDM′isslowly excreted from the fish. The residues of SDM′will be harm to consumersseriously through of the food chain. SDM′has been listed as drug residue monitoringobject at home and abroad. There are little studies of pharmacokinetics and noestablishment of physiological pharmacokinetic model of Sulfadoxine in flounders.This paper systematically studied the pharmacokinetics and residues elimination, andexploringly established the physiological pharmacokinetic model of Sulfadoxine inParalichthys olivaceus and Cynoglossus semilaevis, respectively.In the22±2℃seawater, the pharmacokinetics of SDM′was studied in plasmaand tissues of P. olivaceus after single200mg/kg·body weght dose of SDM′orallyadministration. The results show that the concentrations–curve in plasma, muscle,liver, kidney and skin of P. olivaceus were best described as a two-compartmentmodel. The time to reach maximum concentration is8h in liver and kidney, which is24h in plasma, muscle, skin. It shows that SDM′is rapidly accumulated in liver andkidney after orally administration. The maximum concentration in skin is92.37μg/g,and it shows that the skin is accumulating organ for SDM′. The resdues elimination ofSDM′was studied in plasma and tissues of P. olivaceus after mulity100mg/kg·bodyweght dose of SDM′orally administration for3days. The concentrantions in plasmaand skin are higher, and show that the skin should be regarded as one of residuesobjects. According to elimination regular and maximum residue limits (MRL) ofChina, it suggests that the withdraw time of SDM′in P. olivaceus is no less30days(660tempreture time) under this experimental conditions.In the21±2℃seawater, the pharmacokinetics of SDM′was studied in plasma and tissues of C. semilaevis after single200mg/kg·body weght dose of SDM′orallyadministration. The results show that the concentrations–curve in plasma, muscle,liver, kidney and skin of C. semilaevis were best described as a two-compartmentmodel. The time to reach maximum concentration in plasma, muscle, liver, kidey andskin are8h,12h,6h,6h and8h, respectly. The maximum concentrations are290.74μg/g,72.54μg/g,37.85μg/g,8.51μg/g, and131.77μg/g in plasma, muscle, liver,kidey and skin, respectly. The resdues elimination of SDM′was studied in plasma andtissues of C. semilaevis after mulity100mg/kg·body weght dose of SDM′orallyadministration for3days. The concentrantions in plasma and skin are higher, and theskin is considered as the important residue tissue. According to elimination regularand maximum residue limits (MRL) of China, it suggests that the withdraw time ofSDM′in C. semilaevis is no less37days (777tempreture time) under thisexperimental conditions.A physiological pharmacokinetic model for estimating Sulfadoxineconcentrations from flounders was developed, which include blood compartment,muscle compartment, liver compartment, kidney compartment, skin compartment andother. Sulfadoxine was assumed to be no metabolism. The residue elimination isdescribed by the model. The model parameters are corrected through maximumlikelihood method. And then the sensitivity analysis of model parameters wascompled. It shows that some parameters such as tissue-plasma distribution coefficient,clearance, organ volume ratio are important to the whole model. The model predictedvalue has agreement with the actually measured value. The model can successfullypredict the residue elimination of P. olivaceus. The extrapolation of the developedPBPK to C. semilaevis was studied. The predicted concentrations of the model coulddescribe the residue and elimination. The results shows that the developed PBPK hasa resliable ability to predicted the residue and elimination.In conclusion, the study of pharmacokinetics and establishment of physiologicalpharmacokinetic model of Sulfadoxine in flounders which made a contribution toenrich the basis pharmacokinetic data of the aquatic animals and provided scientificbasis for drug residues evaluation of aquatic products.