Safety Evaluation And Pharmacokinetic Of Ivermectin Microemulsion In Cattle

This thesis studied on safety and pharmacokinetics of target animal for evaluating thesafety and pharmacokinetics of Ivermectin microemulsion．This thesis used1、3、5times of recommended dose and detected hematologicalparameters(white blood cell count， lymphocytes， neutrophils， monocytes， lymphocytespercentage and so on)and biochemical indicators(albumin，globulin，white ball ratio，directbilirubin，total bilirubin，indirect bilirubin，aspartate aminotransferase，alanine aminotransferaseand so on)for evaluating the safety and pharmacokinetics of Ivermectin microemulsion．Theresults showed that hematological parameters and biochemical parameters of all cattles werewithin normal range，the difference of every indicator was not significant(P>0.05)，the targetanimals is safe using at least5times of recommended dose of Ivermectin microemulsion．In the study，the concentration range of plasma drug testing was1～1000ng·ml-1in thedetermination of plasma drug HPLC，the standard curve was y=0.009x+0.073(R2=0.998)，the linear relationship was good in the range of detection，the range of coefficient of variationwas1.89%~4.13%，the recoveries was94.63%~100.02%．The results showed that the methodhad high sensitivity， little interference and good repeatability． The pharmacokineticparameters of Subcutaneous administration group:Cmax=115.01181±6.41253ng·ml-1，Tmax=0.49242±0.05453d，AUC=316.41051±23.37477ng·d·ml-1，K10_HL=1.51437±0.17126，T1/2(α)=0.45461d， T1/2(β)=5.52591d； The pharmacokinetic parameters of intramuscularadministration group： Cmax=121.96218±4.11987ng·ml-1，Tmax=0.23284±0.02354dT1/2(α)=0.45461d，AUC=316.41051±23.37477ng·d·ml-1，T1/2(β)=4.56919d；The pharmac-okinetic parameters of intravenous administration： AUC=60.79578±33.95409ng·d·ml-1，K10_HL=0.35269±0.11165，T1/2(β)=1.96487d．Vivo kinetics of cattle are in line with onecompartment model after administrating by0.2mg·kg-1in subcutaneous， intramuscular，intravenous．The absolute bioavilability of ivermectin microemulsion is55.6%by the way ofsubcutaneous administration and the absolute bioavilability of ivermectin microemulsion is68.66%by the way of intramuscular injection．Compared to other agents reported in theliterature on the same dose，absorption half-time、elimination half–time and peak-reaching time of this drug need shorter time, peak concentration is higher.．The results showed thativermectin microemulsion was effective， Therefore we recommended that ivermectinmicroemulsion should be dosed in subcutaneous or muscle twice or three times every three days．The results showed that Ivermectin microemulsion was safe to target animal．it waseffective，it cound effectively kill the parasite， help to reduce the residual drug in the body andimprove food safety.The research was based on development and clinical application of new、safe and environmental ivermectin drug．...