不同含量伊维菌素长效透皮制剂在家兔体内的药代动力学研究  

Pharmacokinetics of long-acting transdermal agents of different ivermectin content in rabbits

作　　者：刘营营[1] 岳治光 吴宁鹏[3] 闫亚群 刘珍珍[1] 张素梅[1] 菅复春[1] 王荣军[1] 宁长申[1] LIU Yingying;YUE Zhiguang;WU Ningpeng;YAN Yaqun;LIU Zhenzhen;ZHANG Sumei;JIAN Fuchun;WANG Rongjun;NING Changshen(Engineering College of Animal Husbandry and Veterinary Science,Henan Agricultural University, Zhengzhou 450002,China;Henan Amgen Biotechnology Co. ,Ltd. ,Zhengzhou 450002,China;Henan Supervision Institute of Veterinary Drug and Feed,Zhengzhou 450008,China)

机构地区：[1]河南农业大学牧医工程学院,河南郑州450002 [2]河南安进生物技术股份有限公司,河南郑州450002 [3]河南省兽药监察所,河南郑州450008

出　　处：《河南农业大学学报》2020年第2期243-247,共5页Journal of Henan Agricultural University

基　　金：国家现代肉羊产业技术体系建设专项资金项目(nycytx-38)。

摘　　要：研究制备伊维菌素含量分别为0.5%、1.0%、1.5%的长效透皮剂,进行3组相同药量不同体积伊维菌素长效透皮剂在家兔体内的药代动力学试验,研究其代谢过程。优化高效液相色谱-荧光检测器测定血浆中伊维菌素含量的方法,通过绘制标准曲线、对精密度、回收率、检测限和定量限的测定,表明该方法符合生物样品的分析要求。对家兔外耳廓单次均匀喷洒给药,通过血浆中伊维菌素质量浓度随时间的数据变化表明,药物可快速经皮肤吸收入血,发挥效应。伊维菌素含量为0.5%、1.0%、1.5%的伊维菌素长效透皮剂依次记为1、2、3组,通过PKSolver药动学处理软件对数据分析发现,1、2、3组吸收半衰期分别为0.52、0.35和0.75 d;达峰时间分别为1.47、1.13和1.23 d;峰质量浓度分别为91.09、37.61和69.53μg·L^-1;消除半衰期分别为3.55、4.95和4.61 d;平均滞留时间依次为9.995、11.902和6.995 d。药时曲线面积分别为7578.33、5530.75和2542.20μg·d·L^-1。3组药物在家兔血浆内均符合有吸收一室开放模型,且第2组吸收半衰期和达峰时间最短,平均滞留时间最长,效果最好。结果表明,本研究制备的伊维菌素长效透皮剂在家兔体内的血药质量浓度变化平稳,释药时间较长,在体内维持有效药物质量浓度时间长达35 d,有明显的长效作用。Long-acting transdermal agents of ivermectin with concentrations of 0.5%,1.0%and 1.5%were prepared,and pharmacokinetic experiments of the three groups of long-acting transdermal agents of ivermectin with the same dosage but different volumes were conducted to study their metabolic process in rabbits.The method of ivermectin content determination in rabbit plasma by high perfor-mance liquid chromatography-fluorescence detector was optimized.The method was proved to conform to the requirements of analysis in biological samples by drawing standard curves to determine the precision,recovery rate,detection limit and quantitative limit.The drug was sprayed uniformly on the outer auricle of rabbits for a single time,and the data changes of plasma ivermectin concentration over time indicated that the drug could be quickly absorbed through the skin into the blood and give play to effect.The long-acting transdermal agents with ivermectin content of 0.5%,1.0%and 1.5%were successively recorded as groups 1,2,and 3,and data analysis through the PKSolver pharmacokinetic processing software showed that the t1/2ka of groups 1,2,and 3 was respectively 0.52 d,0.35 d and 0.75 d;the Tmax was 1.47 d,1.13 d and1.23 d,respectively;the Cmax was 91.09,37.61and 69.53μg·L^-1,respectively;the t1/2ke was 3.55 d,4.95 d and 4.61 d,respectively;the MRTwas 9.995 d,11.902 d and 6.995 d,respectively;the AUC was 7578.33,5530.75 and 542.20μg·d·L^-1,respectively.The results showed that the long-acting transdermal agent of ivermectin prepared in this study had a stable change in blood mass concentration in rabbits,a long release time,and obvious long-term effects of maintaining effective drug concentration for as long as 35 days in rabbit blood.

关 键 词：伊维菌素 长效透皮剂 高效液相色谱 药代动力学 

分 类 号：S859.79[农业科学—临床兽医学]