Macrocyclic lactone (ML) anthelmintics are the most important class of anthelmintics because of our high dependence on them for the control of nematode parasites and some ectoparasites in livestock, companion animals and in humans. However, resistance to MLs is of increasing concern. Resistance is commonplace throughout the world in nematode parasites of small ruminants and is of increasing concern in horses, cattle, dogs and other animals. It is suspected in Onchocerca volvulus in humans. In most animals, resistance first arose to the avermectins, such as ivermectin (IVM), and subsequently to moxidectin (MOX). Usually when parasite populations are ML-resistant, MOX is more effective than avermectins. MOX may have higher intrinsic potency against some parasites, especially filarial nematodes, than the avermectins. However, it clearly has a significantly different pharmacokinetic profile. It is highly distributed to lipid tissues, less likely to be removed by ABC efflux transporters, is poorly metabolized and has a long half-life. This results in effective concentrations persisting for longer in target hosts. It also has a high safety index. Limited data suggest that anthelmintic resistance may be overcome, at least temporarily, if a high concentration can be maintained at the site of the parasites for a prolonged period of time. Because of the properties of MOX, there are reasonable prospects that strains of parasites that are resistant to avermectins at currently recommended doses will be controlled by MOX if it can be administered at sufficiently high doses and in formulations that enhance its persistence in the host. This review examines the properties of MOX that support this contention and compares them with the properties of other MLs. The case for using MOX to better control ML-resistant parasites is summarised and some outstanding research questions are presented.

中文翻译：

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面对抗蠕虫药发展中莫昔克丁在控制寄生线虫方面的应用前景。

大环内酯（ML）驱虫药是最重要的驱虫药类，因为我们高度依赖它们来控制线虫寄生虫和牲畜，伴侣动物以及人类中的某些体外寄生虫。但是，对ML的抵抗力越来越受到关注。在小型反刍动物的线虫寄生虫中，耐药性在世界各地很普遍，并且在马，牛，狗和其他动物中引起越来越多的关注。在人类的盘尾丝虫中有怀疑。在大多数动物中，首先对阿维菌素（如伊维菌素（IVM））产生抗药性，随后对莫​​昔菌素（MOX）产生抗药性。通常，当寄生虫种群对ML耐药时，MOX比阿维菌素更有效。与阿维菌素相比，MOX对某些寄生虫（尤其是丝状线虫）具有更高的内在效力。然而，它显然具有明显不同的药代动力学特征。它高度分布在脂质组织上，不太可能被ABC外排转运蛋白去除，代谢不良，半衰期长。这导致有效浓度在目标宿主中持续更长的时间。它还具有很高的安全指数。有限的数据表明，如果可以在寄生虫部位长期保持高浓度，则至少可以暂时克服驱虫药的抗药性。由于MOX的特性，如果可以以足够高的剂量和增强其在宿主中持久性的制剂给药，则有合理的前景，即以当前推荐的剂量对阿维菌素具有抗性的寄生虫菌株将由MOX控制。这篇评论检查了支持此竞争的MOX的属性，并将它们与其他ML的属性进行了比较。总结了使用MOX更好地控制耐ML的寄生虫的案例，并提出了一些突出的研究问题。