中文摘要：

【目的】研究联合应用伊维菌素和三氯苯达唑在蠕虫感染绵羊体内的药代动力学特征及相互影响，【方法】借助经典麦克麦斯特法定量检查羊群消化道蠕虫感染基础上选取每克粪便虫卵数大于1500个，且感染强度相近的泌乳期鄂尔多斯细毛羊15只，平均体重为（39.3±3.2）kg，年龄为4周岁。将15只受试羊禁食8 h后随机分成3组，按照预定试验设计给予不同药物：第1组皮下注射伊维菌素（0.2 mg？kg-1），第2组灌服三氯苯达唑混悬液（12 mg？kg-1），第3组皮下注射伊维菌素（0.2 mg？kg-1）的同时灌服三氯苯达唑混悬液（12 mg？kg-1）。分别于给药后第0.75、2、4、8、16、24、36、48、72、120、192和336 h，由颈静脉采集5 mL血样，离心分离血浆，冷冻保存待测。建立检测血浆伊维菌素（IVM）、三氯苯达唑（TCBZ）及其主要活性代谢产物三氯苯达唑亚砜（TCBZSO）浓度的高效液相色谱（HPLC）荧光检测法和紫外检测法，并对每个样品进行甲醇沉淀蛋白，经ODS C18固相萃取柱进行纯化处理后，分别测定各组血浆样品中的IVM、TCBZ及其主要代谢产物TCBZSO的浓度。色谱条件：反相C18柱，InertsilODS-SP（5 μm，4.6×150 mm，I.D.）；流动相为V（甲醇＋乙腈）﹕V（水）=95﹕5；激发波长364 nm，发射波长470 nm；流速为1.0 mL？min-1；柱温为室温；进样量为20 μL。最后将测定血药浓度数据用Phoenix WinNonlin药动学软件按非房室模型方法处理，计算出各试验组每只羊的相关药动学参数，并进行统计学分析。 【结果】血浆样品色谱图中IVM和内标物AVM色谱峰分离良好，保留时间分别为8.73 min和6.16 min，且不受血浆其他干扰峰的影响；TCBZ和TCBZSO以及内标物甲苯咪唑的保留时间分别为10.04、5.53和3.42 min，且在试验分析条件下具有良好的分离度，血浆内源性物质对目标峰没有干扰。对HPLC检测方法的绝对?

英文摘要：

【Objective】 The objective of this study is to illustrate the pharmacokinetic characteristics and interactions of ivermectin and triclabendazole in helminth infected sheep following co-administration. 【Method】 A total of 15 Ordos merino sheep in lactation period of 4 years old, average body weight of （39.3±3.2） kg, naturally infected with gastrointestinal helminth （EPG≥1500） were selected by using McMaster’s method. The testing sheep were randomly divided into 3 treatment groups of 5 sheep in each group. The sheep in groupⅠ were subcutaneously injected with IVM alone （0.2 mg？kg-1）, that in groupⅡ were orally administered with TCBZ alone （15 mg？kg-1）, and that in groupⅢ were combined administrated with TCBZ （15 mg？kg-1 po.） and IVM （0.2 mg？kg-1, sc.）. 5 mL of blood samples were collected from the jugular vein from 0.75, 2, 4, 8, 16, 24, 36, 48, 72, 120, 192 and 336 h after administration, and the concentrations of IVM, TCBZ and TCBZSO in each sample were detected by high-performance liquid chromatography （HPLC） with fluorescence detection and UV detection, respectively. Chromatographic conditions： a reversed-phase C18 column, InertsilODS-SP （5 μm, 4.6×150 mm, I.D.）; mobile phase of V （methanol and acetonitrile）﹕V （water） =95﹕5; excitation wavelength of 364 nm, emission wavelength is 470 nm; the flow rate was 1.0 mL？min-1; column temperature was at room temperature; the injection volume was 20 μL. The pharmacokinetic characteristics were calculated by Phoenix WinNonlin using non-compartmental analysis （NCA） model. 【Result】The results showed that the chromatographic peaks of IVM and internal standard AVM were well separated with retention time of 8.73 min and 6.16 min, which were not influenced by the other interfering peaks of plasma. The retention time of TCBZ, TCBZSO and internal standard of mebendazole were 10.04 min, 5.53 min and 3.42 min, respectively, and well seperated with no interfering peaks. Therefore, the methods establ