Absorption, Tissue Distribution, Metabolism, and Excretion of Moxidectin in Cattle

Zulalian, Jack; Stout, Steven J.; Dacunha, Adrian R; Garces, Temistocles; Miller, Phillip S.

doi:10.1021/jf00038a028

Cited by 84 publications

(90 citation statements)

References 6 publications

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“…Wombats had a higher peak plasma concentration but a shorter plasma elimination halflife than did livestock species, suggesting that moxidectin elimination is less influenced by the lower metabolic rates of marsupials than it is by the amount of body fat (Death et al, 2011). For lipophilic macrocyclic lactones such as moxidectin and ivermectin, subcutaneous fat is likely to influence drug absorption (Oksanen et al, 1995), and these drugs are preferentially distributed into adipose tissue which may act as a drug reservoir and facilitate persistence (Zulalian et al, 1994). In domestic pigs, for example, persistence of macrocyclic lactones is strongly influenced by body condition, with both ivermectin and moxidectin less persistent in thin compared with fat animals (Craven et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Anthelmintic Drugs Against Nematodes Infecting Free-Ranging Eastern Grey Kangaroos, Macropus Giganteus

Cripps

Beveridge

Coulson

2013

Journal of Wildlife Diseases

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ABSTRACT:Effective anthelmintics are valuable tools for biologists conducting manipulative field experiments to examine effects of parasites on wildlife. However, before such experiments are carried out the efficacy of these drugs must be determined. We conducted three field experiments (May 2010-September 2011) on free-ranging eastern grey kangaroos (Macropus giganteus) at a golf course in Victoria, Australia, treating animals with the anthelmintic drugs moxidectin (subcutaneous, 1 mg/kg, 2 mg/kg), ivermectin (subcutaneous, 200 mg/kg), and albendazole (oral, 3.8 mg/kg). After treatment we monitored strongylid fecal egg counts (FECs) over time and assessed anthelmintic efficacy using fecal egg count reduction tests (FECRTs). We also performed a larval development assay (LDA) to evaluate directly the efficacy in the nematode population. Unexpectedly, moxidectin and ivermectin had low efficacy with maximum FEC reductions of 82% and 28%, respectively. However, treatment with albendazole reduced FECs by 100% in all kangaroos and egg counts remained low for up to 3 mo. The results from the LDA supported the FECRTs, with low macrocyclic lactone efficacy and high albendazole efficacy. Macrocyclic lactones, at recommended dose rates, were much less effective against strongylid nematodes in kangaroos than has been reported for domestic herbivores. This may be partly due to pharmacokinetics in the host and partly due to low susceptibility in some of the nematodes infecting eastern grey kangaroos.

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Section: Discussionmentioning

confidence: 99%

The Efficacy of Anthelmintic Drugs Against Nematodes Infecting Free-Ranging Eastern Grey Kangaroos, Macropus Giganteus

Cripps

Beveridge

Coulson

2013

Journal of Wildlife Diseases

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“…Adult emergence rates of C. jessoensis were not significantly different on all days (1, 7, 14, and 21) after treatment between control and treated cattle. Zulalian et al (1994) reported that a peak concentration of moxidectin in the dung of cattle was detected within 3 days after subcutaneous injection at 0.2 mg/kg. It may be conceivable that a pour-on formulation also causes approximately similar results as the highest concentration was reached at day 3 post-treatment and subsequently decreased in this trial.…”

Section: Field Experiments Effects Of Moxidectin On Fly Emergence and mentioning

confidence: 99%

Effects of moxidectin on coprophagous insects in cattle dung pats in Japan

Iwasa

Suzuki

Maruyama

2008

Appl. Entomol. Zool.

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Effects of the antiparasitic drug moxidectin were studied in laboratory and field experiments in Hokkaido, Japan by pour-on administrations (500 mg/kg) on a target pest Haematobia irritans Linnaeus, nontarget coprophagous flies represented by Neomyia cornicina (Fabricius), and the dung beetle Caccobius jessoensis Harold. The concentration of moxidectin excreted into cattle dung was maximum at 3 days post-treatment both in the first and second trials, and then it diminished. No moxidectin was detected on or after day 21 post-treatment in the first trial, and on or after day 28 post-treatment in the second trial. Larval development of H. irritans was hampered from 1 to 7 days post-treatment. No N. cornicina pupated in dung at days 1 and 3 post-treatment, and pupation and emergence rates were reduced in the dung until 7 days post-treatment. There were no significant differences in numbers and weight of brood balls constructed by Caccobius jessoensis in dung from treated and control cattle. Adult emergence rates of C. jessoensis on days 1, 3, 7, 14 post-treatments were not significantly different between control and treated groups, and more than 90% of adult emergence rates were demonstrated in both groups. In the field study using emergence traps, 3,433 (18 families) flies emerged from dung from untreated control cattle and 1,667 (16 families) flies emerged from dung from treated cattle. Notably, the number of Sciaridae spp. (first Experiment) and Sepsis latiforceps Duda and Sphaeroceridae spp. (second Experiment) significantly decreased in dung pats of treated cattle. From 48 dung pats in the field experiments, total dry weight of major coprophagous flies that emerged was 1,741.8 mg in dung from control cattle and 1,170.0 mg in dung from treated cattle, showing 32.8% reduction in treated dung. Emergence rates of C. jessoensis from brood balls recovered from soil beneath dung pats in the field experiments were not significantly different between dung from control and treated cattle on each sampling day (1, 7, 14, and 21 days) post-treatment.

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“…These results may also be associated with greater proportions of MXD accumulating in fat tissue than IVM and DRM, since it has been demonstrated that the concentration of MXD in fat tissue was 90-fold higher than that detected in plasma 28 days following treatment in cattle. 24 The higher fat tissue reservoir of MXD may explain the extended persistence of that molecule compared with that of the avermectins. Moreover, it has been reported that MXD is 100 times more lipophilic than IVM 25 and that the water solubility of MXD (4.3 mg/L) 26 is much higher than that of IVM (0.006 -0.009 mg/L).…”

Section: Discussionmentioning

confidence: 99%

Plasma dispositions of ivermectin, doramectin and moxidectin following subcutaneous administration in rabbits

et al. 2010

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This study evaluated the comparative plasma dispositions of ivermectin (IVM), doramectin (DRM) and moxidectin (MXD) following subcutaneous administration in rabbits. Fifteen New Zealand white rabbits were allocated into three groups of five animals each. The animals in each group received IVM, DRM or MXD by subcutaneous injection at a single dose of 0.3 mg/kg. Blood samples were collected at various times between 1 h and 40 days after treatment and the plasma samples were analysed by high-performance liquid chromatography using fluorescence detection. Moxidectin was absorbed faster from the injection site and reached the peak plasma concentration (C max ) significantly earlier than IVM and DRM. There was no significant difference in C max values among the three molecules, whereas the area under the concentration -time curves of DRM (258.40 ng.d/mL) and IVM (191.62 ng.d/mL) was significantly higher than that of MXD (83.17 ng.d/mL). The mean plasma residence time and terminal half-life (t 1/2lz ) were longer for DRM (7.52 and 4.48 days, respectively) and MXD (8.97 and 8.16 days, respectively) compared with IVM (4.73 and 2.75 days, respectively). Considering the pharmacokinetic parameters for the parent molecules, the persistence of DRM and MXD are significantly longer than IVM and this may have a positive effect on their efficacy in rabbits following subcutaneous administration or utility relating to interdosing interval. Avermectins and milbemycins have been used intensively to control parasites of animals, humans and crops worldwide. Both chemical groups are naturally derived 16-membered macrocyclic lactones 1 produced by the soil dwelling actinomycetes, Streptomyces spp. Milbemycins are structurally related to the avermectins and share physicochemical properties with avermectins. Avermectins and milbemycins have excellent activity against nematodes and have systemic activity against several pathogenic ectoparasites of domestic animals at low dosage rates. Due to the high activity of avermectins and milbemycins against both nematodes and arthropods, they are now classified as 'endectocides'.2 The pharmacokinetic behaviour of avermectins and milbemycins is significantly affected by route of administration, formulation of the drug, and interspecies and interindividual variation.2 These anthelmintics are highly lipophilic substances, and are extensively distributed throughout the body and slowly eliminated through tissues such as liver and fat.3 For this reason a larger volume of distribution (V d ) may be obtained for these compounds compared with other anthelmintics. 4 Rabbits are widely used as laboratory animals for animal experiments. Endectocides are used extralabelly to control particularly ectoparasites, such as mite and mange infestations in rabbits.5212 Pharmacokinetic behaviours of endectocides have been extensively studied in different animal species. Although kinetic dispositions of ivermectin (IVM) have been reported previously, 6,13 very little information is available on the plasma pharma...

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Absorption, Tissue Distribution, Metabolism, and Excretion of Moxidectin in Cattle

Cited by 84 publications

References 6 publications

The Efficacy of Anthelmintic Drugs Against Nematodes Infecting Free-Ranging Eastern Grey Kangaroos, Macropus Giganteus

The Efficacy of Anthelmintic Drugs Against Nematodes Infecting Free-Ranging Eastern Grey Kangaroos, Macropus Giganteus

Effects of moxidectin on coprophagous insects in cattle dung pats in Japan

Plasma dispositions of ivermectin, doramectin and moxidectin following subcutaneous administration in rabbits

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