Phosphate Tilmicosin Pharmacokinetics In Healthy Chickens And Plasma Concentration After Continuous Administration

Tilmicosin is a hydrolyzate of tylosin precursor semi-synthetic macrolide antibiotic belonging to livestock and poultry antibiotics.Not only has the rapid absorption,peak fast,long half-life in blood of drugs,but also widely distributed in the body,the drug tissue penetration and strong?especially in lung tissue and high drug concentra tions in milk?.It can maintain a long time in vivo,in vitro antibacterial spectrum,strong antibacterial activity.Tilmicosin mainly synthetic play a relevant antibacterial effect by inhibiting bacterial protein,binds to the ribosomal 50S subunit suscept ible against nature,through the transfer of a peptide or mRNA shift effect blocking of ribosome the displacement process,hinder the synthesis of the peptide chain extension and protein for growth bacteriostatic agent.Its less toxic part of the reason ma y be that it does not bind to mammalian 80S ribosomes.Tilmicosin phosphate is a phosphate tilmicosin in water.Soluble powder formulationmade by tilmicosin,can be caused by Mycoplasma gallisepticum chicken respiratory infections directly through drinking water administration.By 10%tilmicosin soluble powder and 10%phosphoric acid solution Tilmicosin in vivo pharmacokinetic studies in chickens,and obtains the relevant pharmacokinetic parameters.Find out 10%phosphate tilmicosin soluble powder and 10%tilmicosin tilmicosin solution in healthy chickens laws change over time,and compare the two pharmacokinetic parameters,studies show that 10%phosphoric acid for tilmicosin soluble powder and 10%tilmicosin solution there are differences in pharmacokinetic characteristics.The study not only can guide the development of new formulations of 10%phosphoric acid tilmicosin soluble powder provide the basis for clinical rational drug use,but also to further eliminate the drug dynamic prediction in chickens,vo lume characteristics and eliminate of reference.The experiment established Tilmicosin detection method by HPLC.The mobile phase was tetrahydrofuran:dibutylamine phosphate buffer solution:ultrapure water?55:25:805,V/V/V?,the detection wavelength of 280nm,flow rate 1mL/min,the injection volume was30?L.The results showed that tilmicosin showed a good linear relationship?R²?0.9991?within 0.02⁵?g/mL range,Tilmicosin plasma concentration was low?0.02?g/mL?,medium?0.5?g/mL?high?5?g/mL?,and when the recovery was 83.53%⁹3.11%,intraday variation coefficient of 2.55%-8.61%,day coefficient of variation was6.67%⁷.98%.In this paper,the choice of initial body weight of about 1.1kg three yellow chickens,using a single dose of parallel randomized controlled trial design,24 healthy meat chicken products were randomly divided into two groups,male and female in half,each 12,the first group was treated with 10%phosphate tilmicosin soluble powder,a second group was treated with 10%tilmicosin solution,according to a predetermined time after administration of blood,plasma tilmicosin with dichloromethane-hexane mixture?1:1,v/v?extraction,detection at different time points plasma drug concentration by high performance liquid chromatography UV detecto r.Found plasma concentration-time data were used winnionllin5.2.1 pharmacokinetic analysis software to calculate the pharmacokinetic parameters.10%of phosphate tilmicosin soluble powder and 10%tilmicosin solution after the same dose?15mg/kg?,the former drug-the area under the curve AUC was significantly higher than the latter drugs-under the curve area AUC?P<0.01?,was 2.46±1.35 h·?g/mL and0.79±0.32 h·?g/mL.The former peak concentration C max also significantly higher than the peak concentration of the latter?P<0.01?,respectively,0.277±0.195?g/mL and 0.103±0.044?g/mL,which shows that 10%of phosphate tilmicosin soluble powder representing10%tilmicosin solution has a higher degree of absorption.10%of phosphate tilmicosin soluble powder on chickens elimination half-life t_1/2??h?is significantly less than 10%tilmicosin solution elimination half-life t1/2??h?,respectively,22.74±8.86 h and11.94±7.59h?P<0.01?.Description 10%phosphate tilmicosin soluble powder representing10%tilmicosin solution chickens eliminate slower,longer duration.10%in 10%phosphoric acid was no significant difference?P>0.05?tilmicosin soluble powder peak time Tmax and tilmicosin solution peak time.Description 10%phosphate tilmicosin representing 10%of the phosphate tilmicosin solution more easily and rapidly absorbed through the intestines into the blood.And 10%of phosphate tilmicosin soluble powder C hicken higher degree of uptake,eliminate more slowly.10%tilmicosin solution absorption is relatively poor,the relative bioavailability of only 10%of phosphate tilmicosin 32.1%soluble powder.Continuous administration of the test:10%phosphate tilmicosin soluble powder drinking water for three consecutive days to deliver a dose of 75mg/L,8 day 0:00,10:00,11:00,13:00,15:00.They were collected once a blood test and found that the concentration of tilmicosin time with the extension of water and gradually increase and eventually reach a steady state.Daily peak plasma drug concentrations occurred at about10:00 am,the peak concentration occurred at around 13:00 pm,and then slowly eliminated.Day 3 8:00 am and 10:00 plasma drug concentration was 0.136±0.142?g/mL and 0.139±0.136?g/mL,almost no difference between the two,indicat ing a 10%tilmicosin soluble powder according to 75mg/L water continuous administration of three days,plasma concentrations reached steady state.