Ivermectin has been widely used for antiparasitic drug, and has recently shown a broad-spectrum antiviral activity, including anti-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacokinetic property of ivermectin has not been fully investigated yet. During the plasma preparation, ~32–46% of ivermectin was found in the precipitation. An Liquid Chromatograph-Mass Spectrometer (LC–MS/MS) method for ivermectin in the whole blood samples from beagle dogs was developed and validated. The specificity, accuracy, precision (intra-day and inter-day), matrix effect, recovery and stability of analyte reported here are satisfied with the criteria of Food and Drug Administration (FDA)-Bioanalysis guideline. The oral administrations pharmacokinetics of ivermectin in beagle dogs under fasting and after high-fat meal were studied, and the following parameters were obtained: fasting Cmax, 104 ± 35 μg·L−1; area under the concentration–time curve (AUC0–∞), 2,555 ± 941 h·μg·L−1; and high-fat meal Cmax, 147 ± 35 μg·L−1; AUC0–∞, 4,198 ± 1,279 h·μg·L−1. When the P-gp inhibitor curcumin was also coadministrated orally, Cmax and AUC0–∞ were found to be 177 ± 57 and 4,213 ± 948 h·μg·L−1, respectively. With the comparison to fasting treatment, coadministration of P-gp inhibitor curcumin resulted in increase of the exposure of ivermectin by 1.6-fold, while the exposure after the high-fat diet versus fasting was increased approximately in 1.4-fold, indicating that alternative absorption might play an important role for increasing the exposure of ivermectin for future clinic applications.

中文翻译：

---

伊维菌素B1a在Beagle犬体内的药动学研究

伊维菌素已广泛用作抗寄生虫药物，最近显示出广谱抗病毒活性，包括抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。然而，伊维菌素的药代动力学特性尚未得到充分研究。在血浆制备过程中，在沉淀中发现了约 32-46% 的伊维菌素。开发并验证了比格犬全血样本中伊维菌素的液相色谱-质谱 (LC-MS/MS) 方法。本文报告的分析物的特异性、准确度、精密度（日内和日间）、基质效应、回收率和稳定性均满足美国食品和药物管理局（FDA）生物分析指南的标准。研究了伊维菌素在Beagle犬空腹和高脂餐后口服的药代动力学，得到如下参数：空腹Cmax，104±35μg·L−1；浓度-时间曲线下面积（AUC0-∞），2,555 ± 941 h·μg·L−1；高脂餐Cmax，147±35μg·L−1；AUC0–∞, 4,198 ± 1,279 h·μg·L−1。当同时口服 P-gp 抑制剂姜黄素时，Cmax 和 AUC0–∞ 分别为 177 ± 57 和 4,213 ± 948 h·μg·L−1。与空腹治疗相比，联合给予P-gp抑制剂姜黄素导致伊维菌素暴露量增加1.6倍，而高脂饮食后的暴露量与空腹治疗相比增加约1.4倍，表明替代吸收可能对增加伊维菌素在未来临床应用中的暴露发挥重要作用。