Oral Moxidectin Research Articles

Combined moxidectin and environmental therapy do not eliminate Chorioptes bovis infestation in heavily feathered horses

Chorioptes bovis infestation is a common cause of pastern dermatitis in the horse, with a predilection in draft horses and other horses with thick hair 'feathers' on the distal limbs. The treatment of this superficial mite is challenging; treatment failure and relapse are common. Furthermore, C. bovis infestation may affect the progression of chronic pastern dermatitis (also known as chronic proliferative pastern dermatitis, chronic progressive lymphoedema and dermatitis verrucosa) in draft horses, manifesting with oedema, lichenification and excessive skin folds that can progress to verruciform lesions. An effective cure for C. bovis infestation would therefore be of great clinical value. In a prospective, double-blind, placebo-controlled study, the efficacy of oral moxidectin (0.4 mg/kg body weight) given twice with a 3 week interval in combination with environmental treatment with 4-chloro-3-methylphenol and propoxur was tested in 19 heavily feathered horses with clinical pastern dermatitis and C. bovis infestation. Follow-up examinations over a period of 180 days revealed significantly more skin crusting in the placebo group than in the treatment group. However, no other differences in clinical signs or the numbers of mites detected were found between the two groups. The results of this study suggest that moxidectin in combination with environmental insecticide treatment as used in this study is ineffective in the treatment of C. bovis in feathered horses.

Oral administration of moxidectin for treatment of murine acariosis due to Radfordia affinis

A field trial was conducted to assess the safety and efficacy of oral administration of moxidectin in mice naturally infected with the fur mites Radfordia affinis. The natural infection was diagnosed in two colonies within a large academic institution by direct hair examination. Animals received moxidectin (1% Cydectin, FortDodge) at an oral dosage of approximately 2 mg/kg body weight by micropipette; administration was repeated after 15 days. Forty mice served as an untreated control group. Moxidectin treatment resulted in clinical improvement within a few days after initial treatment, and mites were eradicated from all infested animals at day 30. No side effects or signs of ill health were observed in any of the treated animals. To our knowledge, this is the first report of oral moxidectin for treatment of murine acariosis.

Contribution of lymphatic transport to the systemic exposure of orally administered moxidectin in conscious lymph duct-cannulated dogs

Moxidectin, a macrocyclic lactone (ML), is a potent parasiticide widely used in veterinary medicine and currently under development for use in humans. The contribution of the lymphatic route to the intestinal absorption and transport of moxidectin to the systemic circulation was evaluated in lymph duct-cannulated dogs. Beagle dogs were operated for lymph duct cannulation and were orally dosed with 38 g of corn oil and moxidectin (0.2 mg/kg, n = 3). The lymph and plasma were collected over 24 h and moxidectin and triglyceride concentrations were measured. Similarly, control dogs ( n = 5) were dosed orally with moxidectin and oil and subsequently with moxidectin intravenously. Pharmacokinetic parameters were calculated for moxidectin in the plasma of the dogs. Moxidectin readily accumulated in the lymph and reached a plateau 8 h post-administration, paralleling triglyceride appearance. The percentage of moxidectin recovered in lymph was 22 ± 3% of the total administered dose with 92% being associated with triglyceride-rich particles. The systemic bioavailability of oral moxidectin coadministered with lipid was only 40% in the lymph duct-cannulated dogs compared with 71% in the controls. Our data clearly indicate that the lymphatic transport process contributes significantly to the post-prandial intestinal absorption of moxidectin and subsequently to its systemic bioavailability. The lymphatic transport of moxidectin offers potential strategies based on lipid formulations to improve the bioavailability of MLs when administered orally.

Evaluation of the efficacy of moxidectin in a herd of goats after long-standing consistent use

Two trials were carried out in a herd of goats, where moxidectin had been consistently used for a long-standing period, in order to monitor its field efficacy. Trial I was carried out after the drug had been used for 4 years/13 times and trial II after it had been used for 7 years/23 times. In each trial, 90 goats naturally infested with gastrointestinal nematodes were divided into three groups ( n = 30) and treated as follows: groups I-A and II-A with moxidectin 1% injectable solution at a dose rate of 0.2 mg kg −1 bodyweight, groups I-B and II-B with moxidectin 0.1% oral drench at a dose rate of 0.2 mg kg −1 bodyweight, groups I-C and II-C were kept as untreated controls. Before treatment, mean faecal epg counts were >350.0 for all groups, whilst 14 days later, mean faecal epg counts were 0.0 for groups I-A, II-A, I-B and II-B (percentage reduction after moxidectin administration 100%); 56 days after treatment, mean faecal epg counts were <30.0 for groups I-A, II-A, I-B and II-B (percentage reduction after moxidectin administration >93.5%). Coprocultures revealed the following genera of nematodes in faecal samples Trichostrongylus spp., Teladorsagia spp., Haemonchus contortus, Chabertia ovina, Oesophagostomum spp. and Bunostomum spp. It is concluded that injectable and oral moxidectin are effective against gastrointestinal nematodes in goats at the dose rate of 0.2 mg kg −1 bodyweight.

Enhancement of oral moxidectin bioavailability in rabbits by lipid co-administration.

Moxidectin is a member of the macrocyclic lactone family of drugs widely used for the control of internal and external parasites. Because moxidectin is highly lipophilic, we suspect that lymphatic transport influences the intestinal absorption of oral formulations of the drug. We studied the influence of lipid co-administration on the pharmacokinetics of an oral formulation of moxidectin in rabbits. Ten rabbits were orally administered 0.3 mg kg(-1) moxidectin with or without sunflower oil. Moxidectin and triglyceride were analyzed in plasma over 23 days. Sunflower oil co-administration significantly increased the area under the plasma concentration-time curve of moxidectin (98%, P<0.05) and prolonged its mean residence time from 1.52 days to 2.12 days (P<0.04). Simultaneously, an increase in plasma triglyceride was observed in response to oil administration. It is suggested that lipid administration increases the systemic availability of oral moxidectin by enhancing the extent of intestinal lymphatic transport of the drug. Lipid-based formulations should improve the bioavailability of moxidectin in rabbits.

Resistance to moxidectin and abamectin in naturally acquired Ostertagia circumcincta infections in sheep

AIM: To investigate the occurrence of resistance to macrocylic lactone (ML) anthelmintics by Ostertagia circumcincta in lambs on a sheep and cattle property in the North Island of New Zea- land. METHODS: Thirty lambs were randomly allocated to one of five equal-sized groups, consisting of an untreated control and four treatment groups. The treatments, which were administered at the manufacturer's recommended dose rates, included oral moxidectin, oral abamectin (both at 0.2 mg/kg), an albendazole-levamisole combination, and an albendazole-levamisole-ivermectin combination. Post mortem worm counts were undertaken 7 days after treatment to determine the efficacy of each anthelmintic. RESULTS: The albendazole-levamisole and albendazole-levam-isole-ivermectin combinations both reduced O. circumcincta burdens to zero whereas for moxidectin and abamectin efficacies of only 72% and 29%, respectively, were recorded. CONCLUSIONS: These results clearly demonstrated the occurrence of resistance to MLs by O. circumcincta. Although this is not the first occasion where resistance to this anthelmintic family has been detected in this parasite in sheep in New Zealand, it is the first instance that resistance to either moxidectin or abamectin has been reported.

Resistance to prophylactic treatment with macrocyclic lactone anthelmintics in Teladorsagia circumcincta

Sixty-four Romney ewe lambs were allocated to 12 groups on the basis of liveweight. Four groups ( n=5) were administered oral ivermectin (IVM), 4 ( n=6) oral moxidectin (MOX) and the remaining 4 ( n=5) controlled-release capsules containing IVM (IVM-CRCs). Nine and 10 days later, the groups within each treatment type were challenged with infective-stage larvae (L3) of 1 of 4 different isolates of Teladorsagia circumcincta (two doses each of 5000 L3). The first of these (S) was known to be anthelmintic-susceptible; the second (OR) was a multiple anthelmintic-resistant strain recovered from the field following therapeutic failure of both ivermectin and moxidectin and subsequently maintained in the laboratory without further anthelmintic selection; the third (R) was derived from OR but had been passaged for five generations indoors with each generation being screened with all three broad-spectrum anthelmintic classes; and the fourth (R×S) was an F1 cross between the R and S isolates. As anticipated, because of its limited residual activity, IVM had no significant effect on the establishment, 9 and 10 days post-treatment, of any of the parasite isolates. In contrast MOX, which has greater residual activity, was highly effective at preventing the establishment of the S isolate but showed no significant effect against the OR, R or R×S isolates. The IVM-CRC was also highly effective at preventing the establishment of the S isolate and furthermore it significantly reduced establishment of both the OR and R×S isolates, although it had no significant effect against the R isolate. The results suggest that with respect to the establishment of T. circumcincta L3s following anthelmintic treatment, macrocyclic lactone (ML) resistance is effectively a dominant trait in the presence of MOX, while it behaves as a partially dominant/recessive trait under treatment with IVM-CRCs. The potential implications of this finding in relation to selection for ML resistance in T. circumcincta are discussed.

The effects of ivermectin and moxidectin on egg viability and larval development of ivermectin-resistant Haemonchus contortus

The in vivo effects of ivermectin and moxidectin on egg viability and larval development of ivermectin-resistant Haemonchus contortus were examined over time after anthelmintic treatment of sheep. Twenty merino sheep, (12 months old) were allocated to five treatment groups and infected with ivermectin-resistant H. contortus. Thirty one days later, the sheep were treated with intraruminal ivermectin capsules, oral ivermectin, oral moxidectin or injectable moxidectin at the manufacturer’s recommended dosages, or left untreated. At various times up to 112 days after treatment, faecal egg counts (FEC) were determined and development rates of infective larvae (L3) cultured in faeces or on agar were measured. Eggs in faecal cultures from ivermectin capsule treated sheep showed reduced L3 development percentages in comparison to faecal cultures from untreated sheep. Eggs from ivermectin capsule treated sheep, isolated from faeces, and cultured on agar showed similar L3 development to eggs from control sheep. These results demonstrate an inhibitory effect of excreted ivermectin in faeces on larval development of ivermectin-resistant H. contortus. L3 development in faecal culture from animals receiving oral ivermectin were reduced for only 3 days after treatment. Faecal egg counts and development of L3 larvae in both culture systems from moxidectin treated sheep were low, due to the high efficacy of the drug. Egg counts in moxidectin treated sheep were reduced by approximately 90% 24 h after treatment, before decreasing to almost 100% at 48 h, suggesting that the current quarantine recommendation of holding sheep off pasture for 24 h after treatment may still lead to some subsequent pasture contamination with worm eggs.

Comparison of subcutaneous ivermectin and oral moxidectin for the treatment of notoedric acariasis in hamsters

Thirty hamsters diagnosed with a Notoedres infestation on the basis of their clinical signs and skin scrapings were allocated to three matched groups. The hamsters in group 1 received ivermectin...

Consequences of anthelmintic resistance on liveweight gain of lambs on commercial sheep farms

AIM: To assess the consequences of anthelmintic resistance on commercial sheep farms on liveweight (LW) gains and susceptibility to diarrhoea of growing lambs. METHODS: Five farms with a history of resistance to benzimidazole drenches were selected. On each farm, 150 ewe lambs were randomly allocated to 1 of 3 treatment groups (n=50). Group 1 was treated 5 times at 28-day intervals with oxfendazole (to which nematode resistance had been demonstrated); Group 2 was treated 5 times at 28-day intervals with levamisole or levamisole + oxfendazole (to which nematode resistance had not been demonstrated) and; Group 3 was treated with a combination of slow-release albendazole capsules and oral moxidectin (intended to totally suppress nematode infection). Differentiated faecal egg counts (FECs), FEC reduction tests (FECRT), LW gain and degree of faecal soiling around the breech (dag scores) were determined and compared between groups. RESULTS: Pre-treatment FECs in Group 1 were similar to or slightly lower than those of Group 2. Efficacy of oxfendazole in Group 1 varied between farms and over time within farms, the reduction in FECs after treatment varying from 0 % to >95 %. The genera identified as resistant on each farm also varied over time. Lambs from Group 3 had lower FECs, lower dag scores and higher growth rates than lambs from Group 2, which in turn had higher LW gains than lambs from Group 1. The overall LW gains during the 5 months of the study were 7.03 ±0.27 kg for Group 1,8.33 ±0.27 kg for Group 2, and 9.91 ±0.31 kg for Group 3 (mean ±SEM; means differed significantly from each other, p<0.01). CONCLUSIONS: The decrease in growth rates associated with the continued use of an incompletely effective anthelmintic were surprisingly small in situations where all lambs grazed together.

Selection for anthelmintic resistance by macrocyclic lactones in Haemonchus contortus

Two morphologically marked strains of Haemonchus contortus, CAVRS (smooth-macrocyclic lactone resistant) and McMaster (linguiform-macrocyclic lactone susceptible), were used to investigate the selection for anthelmintic resistance following exposure to ivermectin (IVM), a non-persistent anthelmintic, and a more persistent anthelmintic, oral moxidectin (MOX). Three types of selection were investigated: (1) selection of resident worms at the time of treatment (Head selection); (2) selection of incoming-larvae–post-treatment (Tail selection); and (3) selection of both resident population and incoming larvae (Head+Tail selection). The experimental animals were adult sheep and lambs. In the controls where there was no anthelmintic selection, the proportion of CAVRS in the adult worm population was the same as the proportion in larvae given to both adults and lambs indicating that CAVRS and McMaster H. contortus were equally infective. There was a significant effect of anthelmintic on total worm numbers in adult sheep with MOX treated adults having less worms, but selection type was non-significant. Anthelmintic type had a significant effect on numbers of resistant worms in adult sheep with less resistant worms in the MOX treated groups, but selection type had no effect. Analysis of variance of arcsine-transformed proportions of resistant worms found that the type of anthelmintic had a highly significant effect, with MOX treated adults having a higher proportion of resistant worms, while type of selection was not significant. In the lambs, nil treated controls and IVM Head+Tail and Tail selected groups had similar geometric mean total worm burdens while Head selected had less total worms. In the MOX treated lamb groups the worm burdens were similar within selection type but less than the IVM treated groups. In the lambs, the types of selection that resulted in more resistant worms were IVM Tail, MOX Head+Tail and MOX Tail. Resistant worm numbers were similar in both adult and lamb groups with Head selection by either MOX or IVM. Moxidectin selected out higher proportions of resistant worms than did IVM in the lambs, with Tail and Head+Tail being stronger selectors than Head. Computer simulations were used to estimate the rate at which resistance developed in the field using the information generated in the present study. The anthelmintic treatments used in the simulation followed a strategic parasite control program for H. contortus in which all sheep receive three Closantel (CLS) treatments in summer, all sheep receive a broad-spectrum (BS) drench or capsule at weaning and lambs receive an additional two BS drenches in summer or no further treatment in the case of the capsule. Moxidectin, IVM-capsule and IVM were the broad spectrum anthelmintics simulated. All simulations were run four times assuming high or low efficacy against resident resistant worms and in the presence or absence of CLS resistance. The simulations indicated that the presence of CLS resistance hastened selection for macrocyclic lactone (ML) resistance. While the IVM-capsule will select most rapidly for ML resistance, IVM oral is expected to be least selective. Moxidectin treatment is intermediate, except in simulations with no CLS resistance and when MOX is assumed to be highly effective against resident ML-resistant worms, in which case MOX can be expected to select more slowly than IVM oral treatments.

Efficacy of oral moxidectin gel against benzimidazole-resistant cyathostomes in horses both naturally and artificially infected with a field population

The efficacy of orally administered moxidectin was evaluated against benzimidazole-resistant populations of cyathostomes. The mares used belonged to a herd in which the presence of benzimidazole-resistant small strongyles had been previously demonstrated. First, the mares harboring resistant cyathostomes were identified by fenbendazole treatment and egg hatch assays. The fecal samples containing the small strongly population with the highest LC50 (0.375μg/ml) were cultured in order to prepare infective doses. Thirty-six (36) mares were each experimentally infected with 10,000 resistant third stage larvae. Fifty-seven (57) days later, 30 mares were selected and randomly allocated to three groups of ten according to their fecal epg counts. One group remained untreated, one group received fenbendazole (7.5 mg/kg of body weight) and one group was treated with moxidectin 2% equine gel (0.4 mg/kg). Samples of feces were taken just before treatment and ten days after. Fenbendazole reduced the average number of cyathostome eggs by 40.7%; moxidectin reduced this number by 100%. Compared to the control group, the efficacies were 100% and 0% for moxidectin and fenbendazole, respectively. No adverse reactions to either of the drugs were observed.

Prophylactic efficacy of persistent anthelmintics against challenge with drug-resistant and susceptible Ostertagia circumcincta

Three groups of newly-weaned Romney lambs were given either a standard oral dose of albendazole, a controlledrelease capsule containing albendazole, or a standard oral dose of moxidectin. At 10, 20,...

The persistence of the efficacy of injectable or oral moxidectin against Teladorsagia, Haemonchus and Trichostrongylus species in experimentally infected sheep

The persistence of the efficacy of moxidectin was evaluated against experimental gastrointestinal nematode infections in 55 lambs randomly allocated to 11 equal groups and infected on day 0. Moxidectin 1 per cent injectable solution was administered at a dose rate of 0.2 mg moxidectin/kg bodyweight to five of the groups on days -42, -35, -28, -21 and -14; five other groups were treated with moxidectin 0.1 per cent oral drench at the same dose rate on days -35, -28, -21, -14 and -7, and the 11th group remained untreated as a control. The lambs were infected experimentally with 8000 Teladorsagia circumcincta, 2000 Haemonchus contortus and 10,000 Trichostrongylus colubriformis infective larvae and killed three weeks later. Both formulations of moxidectin showed excellent activity against T circumcincta and H contortus with almost 100 per cent efficacy against the abomasal parasites for up to 35 days after treatment. The efficacy of moxidectin 1 per cent injectable against T colubriformis was much higher (> 99 per cent) than that of the oral drench and it was highly effective up to 21 days after treatment, and gave a moderate reduction in worm burden for up to 35 days after treatment. No adverse reactions to moxidectin were observed in any of the animals.

Comparative efficacy of moxidectin and ivermectin against hypobiotic and encysted cyathostomes and other equine parasites

Efficacies of moxidectin and ivermectin were compared in four groups of eight ponies with natural parasite infections: placebo (Control), oral moxidectin gel at 0.3 mg kg −1 of body weight (Mox 0.3), oral moxidectin gel at 0.4 mg kg −1 of body weight (Mox 0.4), and oral ivermectin paste at 0.2 mg kg −1 of body weight (Ivermectin). Fecal samples were taken 0 and 2 weeks after treatment. Animals were necropsied and worms were collected 2 weeks after treatment. Moxidectin and ivermectin showed similar efficacy (99%) against adult cyathostomes, Strongylus spp., Triodontophorus spp. and Habronema muscae. Both drugs were also more than 98% effective against luminal cyathostome and Oxyuris equi fourth stage larvae (L 4). Neither drug was effective (0–10.1%) against hypobiotic early third stage cyathostome larvae (EL 3). Moxidectin was moderately effective (62.6–79.1%) in removing encysted cyathostome late third stage larvae (LL 3) and L 4, whereas ivermectin was ineffective (0%) against these stages. By contrast, ivermectin was 95.4% effective against Gasterophilus spp. third instar stage, whereas moxidectin was only 0–20.4% effective.

Comment on anthelmintic use in goats and the effect of route of administration

Abstract Extract In a recent publication in this journal(1) Bailey, KM. 1994. Anthelmintic use in goats and the effect of route of administration. New Zealand Veterinary Journal, 42: 37–8. [Taylor & Francis Online], [Web of Science ®] , [Google Scholar], administration of oral and injectable moxidectin (Vetdectin, Cyanamid N.Z. Ltd) to goats was found to result in faecal egg count reductions of 0% and 84% respectively, in infections that were predominantly composed of Ostertugia spp. The author considered that these results raised issues pertaining to the relative effectiveness of different routes of anthelmintic administration in goats and further suggested, as the animals were suffering from “water belly” at the time of treatment, that the occurrence of this syndrome may also have affected the pharmacodynamics of the anthelmintic.