In ViVO Pharmacokinetics And Pharmacodynamics Modeling Of Baicalin Against Mycoplasma Gallisepticum In Chicken

Mycoplasma gallisepticum?MG?,also known as Mycoplasma gallisepticum,is one of the four major pathogens that harm the global poultry industry.Its clinical manifestations are mainly tears,sneezing,increased nasal secretions and other respiratory symptoms.Mycoplasma gallisepticum has a slow course of infection,and is often coinfected with other bacteria.Once the chicken group is infected,it will be passed on from generation to generation,which is difficult to remove.At present,vaccination and antibiotics are used to prevent Mycoplasma gallisepticum infection in clinic.However,due to the large amount of antimicrobial drugs used in daily medication,,the variation of strains is very large,and the limitation of culture conditions,so the treatment of the disease needs to develop new drugs.Because of the advantages of traditional Chinese medicine,such as safety,non-toxic,easy to obtain and wide range of functions,people pay more and more attention to its application in veterinary clinics..Among them,Baicalin,as the main active component of the traditional Chinese medicine Scutellaria baicalensis,is well known by researchers because of its wide application.Earlier in this laboratory,it was confirmed that baicalin can effectively inhibit Mycoplasma gallisepticum infection in chicks.The purpose of this study is to establish PK/PD synchronous model to evaluate the efficacy of Baicalin in the treatment of Mycoplasma gallisepticum infection,and to lay a theoretical foundation for the application of Baicalin in clinical treatment.In this study,we first successfully replicated the chick Mycoplasma gallisepticum infection model established in the early stage,infested chickens with three different concentrations of Baicalin,and analyzed the pharmacokinetic characteristics of Baicalin in infected chickens;The drug regimen was used to treat infected chickens,and the antibacterial effect of Baicalin on Mycoplasma gallisepticum was investigated;a PK/PD synchronization model of Baicalin on Mycoplasma gallisepticum was constructed.The specific contents of this study are as follows:?1?The microbial dilution method was used to determine the minimum inhibitory concentration?MIC?of Baicalin on Mycoplasma gallisepticum.The results showed that the MIC value of Baicalin against MG_R strain was 31.25?g/m L.Infect the 7-day-old chicks by inoculating the MGR strain bacterial solution through the air bag,observe the clinical symptoms on the 3rd day after infection,and perform necropsy,pathological examination and PCR identification.The results showed that the MG infection model of chicks was successfully reproduced and the course of disease was moderate,which was suitable for the follow-up treatment of this study.?2?After chickens were infected with MG for 12 hours,Baicalin of different concentrations?200,400,600 mg/kg?was administered by gavage,and plasma and lung tissues were obtained at different time points after administration.The extraction method of Baicalin in chicken samples was established.The concentration of Baicalin in plasma and lung tissue of infected chicken was determined by ultra-high performance liquid chromatography?UPLC?.The data obtained was processed by Winnonlin pharmacokinetic software.The results showed that in the dose range of this study?200?600 mg/kg?,the dose of Baicalin was positively correlated with Cmax and AUC₂₄,and the correlation was good,with correlation coefficients R²=0.9959 and R²=0.9972.?3?Eight different doses were used to treat the infected chicken.The infected chickens were sacrificed and lung tissues were collected 24 hours after the last administration,The MG colonization in the lung tissue of the infected chicken was quantitatively detected by real-time PCR.Combined with plasma pharmacokinetic parameters and MIC values in vitro,Sigmoid Emax model was used to fit the data of antibacterial activity in vivo.According to the results of this study,when AUC₂₄/MIC is 0.62,Baicalin has antibacterial effect,MG decreases by 0×Log₁₀ CCU/m L;when AUC₂₄/MIC is 1.33,Baicalin has antibacterial effect,MG decreases by 2×Log₁₀ CCU/m L;when AUC₂₄/MIC is 1.49,Baicalin has eradication effect,MG decreases by 3×Log₁₀ CCU/m L.To sum up,this experiment successfully constructed a synchronous pharmacokinetic and pharmacodynamic model of Baicalin in chickens infected with Mycoplasma gallisepticum,analyzed the pharmacokinetic characteristics of Baicalin in chickens infected with MG,evaluated the relationship between the dosage and efficacy of Baicalin,and provided theoretical basis for clinical treatment of respiratory diseases in chickens.