Simultaneous Pharmacokinetic And Pharmacodynamic Model Of Ceftiofur In E.coli Infected Ducks

Escherichia coli?E.coli?is a disease easily infected by ducks,chook and other poultry,which seriously affects the development of poultry breeding industry.If E.coli is mixed with other pathogens,it will cause greater economic losses to the poultry industry.Cefuroxime is a third-generation cephalosporin antibiotic,which has the characteristics of wide antibacterial spectrum and strong antibacterial activity,and has been widely used in the treatment of bacterial infectious diseases in swine,cattle,chickens and other animals.Long-acting cefotifurme preparation has many advantages,such as effective control of drug release,prolongation of drug delivery interval,reduction of drug delivery times,and reduction of animal stress response.However,so far there have been no reports on pharmacokinetics and pharmacodynamics of cefotifurme in Ecoli infected ducks.In this study,a pharmacokinetic and pharmaceutical?PK-PD?synchronous model study of long-acting cefotifuran in escherichia coli infected ducks was planned,with a view to obtaining PK-PD parameters,and providing theoretical guidance for the formulation of rational drug administration scheme of long-acting cefotifuran for duck Escherichia coli disease treatment.This study adopts the method of chest muscle injection of E.coli bacteria liquid copy duck Escherichia coli infection model,the results show that the duck breast muscle injection concentration of 1 x 10¹⁰CFU/m L of E.coli bacteria liquid 1 m L,the microbial load of the duck blood of 10⁷CFU/m L,microbial load and the stability,according to this method to copy the disease model of duck only can be used for subsequent experimental study.In this study,the minimum inhibitory concentration?MIC?and minimum bactericidal concentration?MBC?values of Cefuroxime against Escherichia coli CVCC1569 in duck serum matrix and broth?MHB?culture were determined,and the minimum anti-mutation concentration?MPC?was determined by AGAR method.The results showed that the CVCC1569MIC value of cefuroxime against Escherichia coli was 0.25?g/m L,the MBC value was 0.5?g/m L and 1?g/m L,and the MPC value was 8?g/m L,respectively,in culture medium and duck serum.The in vitro bactericidal curve of Cefotifurme against Escherichia coli CVCC1569 was plotted.When the drug concentration was greater than 2?g/m L,the bacteria could be completely killed after 2 h.When the concentration of the drug was 1?g/m L,the bacteria could be killed after 4 h.When the concentration of the drug was 0.5?g/m L,the sterilization time was significantly prolonged,and the bacteria could be killed completely after 8 h.When the concentration of the drug is less than 0.25?g/m L,it cannot inhibit the growth of bacteria.Plasma was collected at different time points after subcutaneous injection of long-acting cefotifurme into ducks infected with Escherichia coli.Plasma concentrations were determined by HPLC.Pharmacokinetic data were analyzed by using 3p97pharmacokinetic software.The results showed that the area under the curve?AUC?,peak concentration?Cmax?and time when the drug concentration was greater than MIC?T>MIC?were 6.849?g/m L·h,2.015?g/m L,and 32%,respectively,when the drug was administered at 1?1.5 and 3 mg/kg b.w dose in escherichia coli infected ducks.9.993?g/m L·h,2.78?g/m L,42%;11.051?g/m L·h,4.314?g/m L,55%.After the same method was used,the blood was collected at different time points for bacterial colony counting,and the bactericidal curves of cefotifuran on escherichia coli infected ducks were plotted.It was found that the antibacterial effects of 1?1.5and 3 mg/kg b.w dose of long-acting cefuroxime were-2.73,-3.29 and-3.848 lg CFU/m L,respectively.The PK-PD model was constructed by using Winnonlin 5.2.1 software to fit the pharmacokinetic parameters and pharmacodynamic data of different dose groups.The results showed that the optimal pk-pd parameter of long-acting cefuroxime for duck escherichia coli was T>MIC and its correlation coefficient was 0.9950.The second was Cmax/MIC,with a correlation coefficient of 0.991.The correlation coefficient of AUC/MIC was the lowest,0.9493.The T>MIC of long-acting cefuroxime was 3.24%,37.68%and 58.98%,respectively,when it inhibited,killed and cleared Escherichia coli infected in ducks.