Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic.
Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic.
Ecotoxicol Environ Saf. 2019 Mar;169:944-949. doi: 10.1016/j.ecoenv.2018.11.097. Epub 2018 Dec 2.
Ivermectin (IVM), a macrocylic lactone from the avermectin family, is a potent broad-spectrum anthelmintic drug widely used in veterinary as well as human medicine. Although the health benefits of IVM treatment are particularly important, this drug also represents an environmental pollutant with potentially negative effects on many non-target species. To evaluate the ecotoxicological risk of IVM administration to livestock, information evaluating achievable environment-reaching concentration is needed. Therefore, the present study was designed to determine the excretion profile of subcutaneously administered IVM in sheep. The standard recommended dose of IVM (0.2 mg kg b.w.) was used. UHPLC/MS/MS was used for the analysis of IVM faecal concentration. In addition, the effect of IVM on seed germination and early roots growth of white mustard (Sinapis alba L.) was evaluated in order to estimate the potential phytotoxic effect of IVM. Based on the obtained results, the parameters of IVM pharmacokinetics (maximum concentration (c), time to achieve maximum concentration (t), mean residence time (MRT), area under the curve (AUC)) were calculated. IVM elimination in sheep was slow, but faster than the elimination reported previously in cattle. Great interindividual differences were also observed. A two-peak profile of concentration curves indicate the importance of the active efflux of IVM via enterocytes. A "seed germination and early roots growth" test revealed significant IVM phytotoxicity (20% inhibition of root growth) even at 50 nM concentration, a level which may be found in the environment. This newly demonstrated phytotoxicity of IVM together with its well-known toxicity to invertebrates should be taken into account, and thus animals treated with IVM should not be kept in pastures, especially not in sites with high ecological value.
伊维菌素（IVM）是阿维菌素家族的大环内酯类化合物，是一种广泛应用于兽医和人类医学的强效广谱驱虫药物。虽然 IVM 治疗的健康益处尤其重要，但这种药物也代表了一种环境污染物，可能对许多非目标物种产生负面影响。为了评估 IVM 对家畜给药的生态毒理学风险，需要评估评估可达到的环境浓度的信息。因此，本研究旨在确定皮下给予绵羊 IVM 的排泄情况。使用了推荐的 IVM 标准剂量（0.2mg/kg 体重）。使用 UHPLC/MS/MS 分析 IVM 的粪便浓度。此外，还评估了 IVM 对白芥菜（Sinapis alba L.）种子发芽和早期根系生长的影响，以估计 IVM 的潜在植物毒性作用。根据获得的结果，计算了 IVM 药代动力学的参数（最大浓度 (c)、达到最大浓度的时间 (t)、平均驻留时间 (MRT)、曲线下面积 (AUC)）。IVM 在绵羊中的消除缓慢，但比以前在牛中报道的消除速度快。还观察到很大的个体间差异。浓度曲线的双峰谱表明 IVM 通过肠细胞主动外排的重要性。“种子发芽和早期根系生长”试验显示，即使在 50nM 浓度下，IVM 也具有显著的植物毒性（根生长抑制 20%），这一浓度可能在环境中存在。IVM 新表现出的植物毒性与其对无脊椎动物的已知毒性应加以考虑，因此不应将用 IVM 治疗的动物饲养在牧场中，尤其是在具有高生态价值的地方。
