Optimization Of Tilmicosin Solution And Comparative Study Of Its Pharmacokinetics In Sanhuang Chicken

Tilmicosin is the earliest successful derivative of Tylomycin developed by Elanco Animal Health Company in the UK.It belongs to the macrolide antibiotics and has been put into use in many countries around the world.Currently,there are multiple mature preparation processes.This article mainly optimizes the formula of a Tilmicosin solution and conducts a quality study of Tilmicosin solution according to the content of the"Veterinary Pharmacopoeia of the People’s Republic of China".It examines whether Tilmicosin solution will quickly degrade when dissolved in water during practical production applications.At the same time,this experiment conducted a pharmacokinetic study on Tilmicosin and a commercially available Tilmicosin solution in Sanhuang chickens to observe whether there were any pharmacokinetic differences between them.This experiment optimized the formula of Tilmicosin solution,prepared three p H Tilmicosin solutions for comparison,conducted accelerated testing,and tested the content of three p H Tilmicosin solutions according to the content detection method under the Tilmicosin solution item in the Veterinary Pharmacopoeia of the People’s Republic of China.When using Tilmicosin in practice,it needs to be mixed with water and administered evenly.In this experiment,HPLC method was used to detect the content and stability of Tilmicosin in water,which has certain guiding significance for practical application.The HPLC method was readjusted to establish an HPLC method for detecting the content of Tilmicosin in chicken blood plasma.The methodology was validated through indicators such as recovery rate,accuracy,precision,and regression curve.Afterwards,two groups of Sanhuang chicken（n=12）were orally administered with self-made Tilmicosin solution and a commercially available Tilmicosin solution at a dose of 12mg/kg.bw.Blood samples were collected at 0 hours,0.25 hours,0.5 hours,0.75 hours,1hour,2 hours,4 hours,6 hours,8 hours,10 hours,12 hours,18 hours,and 24 hours after administration,and the plasma was deproteinized with acetonitrile.The previously established blood drug detection method was used to detect Tilmicosin in the blood samples of 24 Sanhuang chicken by HPLC,The measured results were processed using Graphpad Prism 8 and Winnolin 5.2 pharmacokinetic software,drug time curves were plotted,pharmacokinetic parameters were analyzed,and pharmacokinetic differences between the two Tilmicosin solutions in Sanhuang chickens were compared.The 6-month accelerated test showed that the stability of Tilmicosin solution was high in the p H range of 4-5.In practical use,it would degrade within 24 hours when dissolved in water,and should be used as soon as possible;The pharmacokinetic differences between self-made and commercially available Tilmicosin solutions in Sanhuang chickens were not significant（P>0.05）.After oral administration of self-made Tilmicosin solution,Sanhuang chickens could reach the peak concentration of the drug at0.979±0.345 hours.The commercially available Tilmicosin solution reached the peak concentration at 1.083±0.444 hours,with a slightly earlier peak time.The peak concentration C_maxof the two were 2.36±0.26μg/m L and 2.39±0.27μg/m L,respectively,with a small difference in peak concentration,The AUC under the drug time curve of self-made Tilmicosin solution is 14.28±2.02μg/m L/h,AUC of a commercially available temicoxacin solution is 15.79±2.30μg/m L/h,with a small difference between the two;The average retention time is 8.69±0.61 hours and 9.21±0.65 hours,respectively.Therefore,in clinical use,rational administration can be carried out according to the instructions and methods.