The Pharmacokinetics And Residue Of Ivermectin Microemulsion In Sheep

This thesis studied on the pharmacokinetics and residual depletion of a new preparation of ivermectin microemulsion in sheep.The research has been established a method to detect the concentration of the new preparation of ivermectin microemulsion in plasma of the sheep,obtained the pharmacokinetic parameters and analyzed the characteristics of pharmacokinetics.The study established a method to detect the residual of ivermectin in different tissues of the sheep,obtained the elimination of residual in different tissues,established the withdrawal time of the ivermectin microemulsion.The study established a method using HPLC-MS/MS to detect the concentration of ivermectin in plasma. The experimental results show that the pretreatment method is simple and effective,the LOD is0.3 ng/mL and the LOQ is 0.5ng/mL,the standard curve linearity is fine,average recovery rate is greater than 90%,Intra-day and Inter-day precision are all less than 10%.The method has little interference,good reproducibility and high sensitivity.Give the drug to the sheep in 3 ways,such as subcutaneous,intramuscular and intravenous injection.The results show that the subcutaneous administration group’s AUC is 1343.07±101.17 h·ng/mL,peak concentration Cmax is 50.61±2.96 ng/mL,time to peak Tmax is 7.14±0.80 h,absorption half time T1/2(α) is 4.46 h,elimination half life T1/2(β) is 25.45h;the intramuscular administration group’s AUC is 1814.24±56.06h·ng/mL,Peak concentration Cmax is70.34±1.89ng/mL,time to peak Tmax is 3.99±0.20 h,absorption half time T1/2(α) is 4.52 h,elimination half life T1/2(β) is 20.08 h.The absolute bioavailability of intramuscular injection and subcutaneous injection are 91.33% and 67.62%.Compared the different ways of administration we found that intramuscular injection has a higher peak concentration,faster time to peak,higher bioavailability than subcutaneous injection.This study established a method using HPLC-MS/MS to detect the residual of ivermectin in sheep tissues.Samples are extracted with acetonitrile,purified by Alumina-B solid phase extraction(SPE).The results indicate that the ivermectin matrix matched the standard curve in the 1 ~ 3000ng/mL drug concentration range,R2 are all greater than 0.999,the standard curve linearity is fine. The LOD of the neck muscles,kidney,fat,longissimus muscle and liver tissues is 0.3 ng/mL,and the LOQ is 0.5ng/mL.The LOQ of the method is lower than the EU,the United States and China’s regulations for ivermectin residue limits. Average recovery rate is greater than 70%,Intra-day and Inter-day precision are all less than 10%.Thus,the HPLC-MS/MS method is simple,rapid,accurate and high sensitivity to detect the residual of ivermectin in sheep tissues.Fit the measured data by the software WT1.4,The withdrawal time of the neck muscles is 14.71 d,The withdrawal time of the liver is 18.27 d,The withdrawal time of the kidney is 17.49 d,The withdrawal time of the fat is 18.61 d,The withdrawal time of the back muscle length is 12.90 d. According to the elimination of data for the target animal sheep,combined with the calculation of the software WT1.4,suggest that the withdrawal period of ivermectin in sheep is 19 day.This study lays a foundation for new drug evaluation and clinical application of the ivermectin microemulsion...