4种酒石酸泰万菌素预混剂在猪体内的对比药代动力学研究  

Comparative pharmacokinetic study of four tylvalosin tartrate premixes in pigs

作　　者：李江 姚学强 代国年 程富胜[1] 李冰[1] 周雅馨 白玉彬 王玮玮 翟斌涛 魏小娟[1] 郭丽华 张继瑜[1] 周绪正[1] LI Jiang;YAO Xueqiang;DAI Guonian;CHENG Fusheng;LI Bing;ZHOU Yaxin;BAI Yubin;WANG Weiwei;ZHAI Bintao;WEI Xiaojuan;GUO Lihua;ZHANG Jiyu;ZHOU Xuzheng(Lanzhou Institute of Animal Husbandry and Veterinary Medicine,Chinese Academy of Agricultural Sciences,Lanzhou 730050,China;Shandong Dezhou Shenniu Pharmaceutical Co.,Ltd.,Dezhou 253034,China)

机构地区：[1]中国农业科学院兰州畜牧与兽药研究所,甘肃兰州730050 [2]山东德州神牛药业有限公司,山东德州253034

出　　处：《畜牧与兽医》2025年第4期51-59,共9页Animal Husbandry & Veterinary Medicine

基　　金：甘肃省重点研发计划项目(23YFNA0001);舟曲县黑土猪产业质量标准体系建设项目(ZQJY-ZC-2023-048)。

摘　　要：旨在比较4种国内自研的酒石酸泰万菌素预混剂(受试制剂)和爱乐新(参比制剂)在猪体内的药代动力学特征,根据药代动力学参数评价5种制剂间的相对生物利用度,遴选出生物利用度更高的制剂。采用平行试验设计方法,选取30头杜长大三元杂交猪,随机分为5组,公母各半,按25 mg/kg剂量,以经口灌胃单次给药的方式,分别给予受试制剂和参比制剂。采用超高效液相色谱-串联质谱(UPLC-MS/MS)方法测定血药浓度,使用WinNonlin软件中非房室模型进行分析,计算5种制剂的药代动力学参数和相对生物利用度。药代动力学结果显示:受试制剂1~4号药和参比制剂爱乐新的消除半衰期(T_(1/2))分别为(4.40±1.98)、(5.03±1.39)、(4.73±1.42)、(1.26±0.32)和(3.52±0.86)h;达峰时间(T_(max))分别为(4.00±0.00)、(0.50±0.00)、(0.90±0.22)、(0.56±0.13)和(0.50±0.00)h;达峰浓度(C_(max))分别为(51.86±8.95)、(111.00±4.51)、(37.95±5.28)、(92.13±2.65)和(147.71±29.47)ng/mL;药时曲线下面积(AUC_(last))分别为(260.15±29.63)、(336.68±9.41)、(227.93±11.56)、(204.33±4.83)和(300.48±32.09)h·ng/mL;1~4号药相对生物利用度(F)分别为86.58%、112.05%、75.85%、68.00%。综上,本试验建立的泰万菌素UPLC-MS/MS检测方法高效、准确、可靠,可用于泰万菌素在动物体内的药物动力学分析;药代动力学参数结果表明,酒石酸泰万菌素预混剂在猪体内具有吸收迅速、达峰时间短、消除较快、血液中平均滞留时间较短等特征;对比4种国内自研酒石酸泰万菌素预混剂和进口药爱乐新药代动力学参数,以国产酒石酸泰万菌素预混剂2号药T_(1/2)最长、T_(max)最短、AUC_(last)最大、F最高,综合评价最佳,具有临床应用价值和进一步开发潜力。This study aimed to compare the pharmacokinetic characteristics of four domestically developed tylvalosin tartrate premixes(test⁃ed formulations)and the imported drug ailoxin(reference formulation)in pigs.The relative bioavailability of the five formulations was evalu⁃ated based on pharmacokinetic parameters to select the formulation with higher bioavailability.Using a parallel experimental design method,30 ternary crossbred pigs(Duroc×Landrace×Yorkshire)were selected and randomly divided into 5 groups,with an equal distribution of males and females in each group.The test formulations and the reference formulation were administered as a single dose via oral gavage at a dose of 25 mg/kg.Then,the blood concentration in the pigs was determined using the UPLC-MS/MS method and analyzed by a non-atrial model using the WinNonlin software to calculate the pharmacokinetic parameters and relative bioavailability of the five formulations.The phar⁃macokinetic results showed that the elimination half-lives(T_(1/2))of the subjected formulations 1 to 4 and the reference formulation of Ailoxin were(4.40±1.98),(5.03±1.39),(4.73±1.42),(1.26±0.32),and(3.52±0.86)h,respectively;that the time points to reach the peak values(T_(max))were(4.00±0.00),(0.50±0.00),(0.90±0.22),(0.56±0.13),and(0.50±0.00)h,respectively;that the peak concentrations(C_(max))were(51.86±8.95),(111.00±4.51),(37.95±5.28),(92.13±2.65),and(147.71±29.47)ng/mL,respec⁃tively;that the areas under the curve(AUC_(last))at time of administration were(260.15±29.63),(336.68±9.41),(227.93±11.56),(204.33±4.83),and(300.48±32.09)h·ng/mL,respectively;and that the relative bioavailability(F)was 86.58%,112.05%,75.85%,and 68.00%,respectively.These results indicated that the UPLC-MS/MS method established in this experiment was highly effi⁃cient,accurate and reliable,and could be used for the determination of the concentration of tylvalosin.The parameter results showed that tyl⁃valosin tartrate premix possessed the characteristics of rapid absorption,

关 键 词：泰万菌素 对比药代动力学 猪 超高效液相色谱-串联质谱 相对生物利用度 

分 类 号：S859.796[农业科学—临床兽医学]