沃尼妙林在猪体内的生物利用度及药代动力学研究  

Bioavailability and pharmacokinetics of valnemulin in pigs

作　　者：曾东平[1] 严楚[1] 孙永学[1] 方炳虎[1] 曾振灵[1] 刘雅红[1] 

机构地区：[1]华南农业大学兽医学院国家兽药残留基准实验室,广东广州510642

出　　处：《中国兽医科学》2010年第10期1076-1079,共4页Chinese Veterinary Science

基　　金：国家"十一五"科技支撑计划项目(2006BAD31B01)

摘　　要：选用体重20kg左右的大×长二元健康阉公猪8头,按双周期、双交叉试验设计,进行静脉注射及内服沃尼妙林(10.5mg/kg)的药代动力学研究。采用液相色谱-串联质谱法测定猪血浆中沃尼妙林的浓度,用3P97药代动力学程序处理血浆药物浓度-时间数据。结果,健康猪静脉注射给药的药时数据适合一级吸收二室模型,主要药代动力学参数为:t1/2α=0.21h±0.07h,t1/2β=3.09h±1.09h,Vd=3.64L/kg±0.43L/kg,CLB=0.83L/(kg·h)±0.29L/(kg·h),AUC=12.93mg/L·h±4.57mg/L·h。健康猪内服给药的药时数据适合一级吸收一室开放模型,主要药代动力学参数为:t1/2ka=0.76h±0.05h,t1/2kel=2.19h±0.31h,tmax=1.70h±0.04h,Cmax=1.35μg/mL±0.06μg/mL,AUC=7.34mg/L·h±0.52mg/L·h,F=56.62%±3.75%。结果表明,沃尼妙林在健康猪体内的药代动力学特征是:内服吸收迅速,血药浓度达峰时间短,药物峰浓度高,绝对生物利用度较高,但有效血药浓度维持时间短,药物消除较快。Eight healthy crossed-bred（Yorkshire×Landrance）pigs,weighing an average of 20kg,were randomly assigned to two dietary treatments with a randomized two period cross-over design following single intravenous（i.v.）,oral administration of the drug at the dose of 10.5mg/kg according to body weight. Blood samples were collected at different intervals after administration and valnemulin concentrations were determined by LC-MS/MS method.Then the pharmacokinetics process was evaluated by Pharmacokinetics Program 3P97.These results showed that the valnemulin concentration-time data were fitted to a two-com- partment open model with first-order absorption after single i.v.dosing of valnemulin in healthy pigs and the resulting main pharmacokinetic parameters were computed as follows：t1/2α=0.21h±0.07h,t1/2β=3.09 h±1.09h,Vd=3.64L/kg±0.43L/kg,CLB=0.83L/（kg·h）±0.29L/（kg·h）,AUC=12.93mg/L·h ±4.57mg/L·h.For the oral dosing of valnemulin in healthy pigs,the drug concentration-time data were fitted to a one-compartment open model with first-order absorption.The main pharmacokinetic parameters were calculated as follows：t1/2ka=0.76h±0.05h,t1/2kel=2.19h±0.31h,tmax=1.70h±0.04h,Cmax=1.35 μg/mL±0.06μg/mL,AUC=7.34mg/L·h±0.52mg/L·h,F=56.62%±3.75%.In conclusion,valnemulin was quickly absorbed,shortly reached tmaxand in high Cmax with good bioavailability,but shortly maintained effective blood drug concentration and quickly eliminated after oral administration in pigs.

关 键 词：沃尼妙林 液相色谱-串联质谱法 生物利用度 药代动力学 猪 

分 类 号：S859.7[农业科学—临床兽医学]