Abstract:
: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.
journal_name
Int J Parasitol Drugs Drug Resistauthors
Prichard RK,Geary TGdoi
10.1016/j.ijpddr.2019.06.002subject
Has Abstractpub_date
2019-08-01 00:00:00pages
69-83issn
2211-3207pii
S2211-3207(19)30059-4journal_volume
10pub_type
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2017.10.002
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章,评审
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.02.006
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.08.002
更新日期:2020-12-01 00:00:00
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.10.002
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2016.06.004
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.10.004
更新日期:2020-12-01 00:00:00
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.09.006
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