moxidectin and doramectin

The objective of this study was to evaluate two different gastrointestinal nematode treatment regimens. Fecal egg counts (FECs), proportion of nematode genera, weight gain, body condition score and reproductive indices (estrous cyclicity, conception and pregnancy rates) were evaluated in yearling heifers after imposing two treatment regimens for gastrointestinal nematodes: T1 = 306 calves treated in May and November with 3.5 % doramectin (700 μg/kg) and August (Aug) with saline solution; and T2 = 307 calves treated in May with 3.5 % doramectin (700 μg/kg), in August with 1% moxidectin (200 μg/kg) and in November with 3.5 % doramectin (700 μg/kg). The animals were weighed, and feces were collected for conducting FECs and coproculture. There was imposing of three fixed-time artificial inseminations (TAIs), and estrous cyclic and pregnancy statuses were determined. Cooperia was the most frequent genus detected in both groups. Heifers of the T2, as compared to those in the T1 group, had fewer FECs in November (P ≤  0.05) and greater weight gain and average daily weight gain (P ≤  0.05) from August to November. There tended to be more heifers of the T2 than T1 group estrous cycling (P =  0.07) at the beginning of the breeding season as well as greater pregnancy rates (P =  0.03) and conception rates (P =  0.03) as a result of the second FTAI. The results indicate there is greater reproduction outcomes as a result of strategic control of gastrointestinal nematodes in yearling Nellore heifers using the T1 as compared with T2 treatment regimen.

Topics: Animals; Anthelmintics; Cattle; Cattle Diseases; Estrous Cycle; Feces; Female; Ivermectin; Macrolides; Nematode Infections; Parasite Egg Count; Pregnancy; Weight Gain

The focus of gastro-intestinal parasite control in the sheep industry is increasingly on finding a balance between maintaining productivity of the flock whilst minimising selection for anthelmintic resistance to preserve anthelmintic efficacy for the future. Periparturient ewes represent the major source of gastro-intestinal parasites for growing lambs and are therefore a priority for parasite control. This study examines the impact on ewe faecal egg counts (FECs), lamb FECs, lamb daily live weight gains (DLWGs) and pasture larval counts of treating groups of ewes two weeks prior to lambing with either, a long-acting moxidectin treatment, short-acting doramectin or control. Six groups of twenty ewes were allocated to individual paddocks, two groups allocated to each treatment, and weekly faecal sampling was performed throughout from the ewes and from six weeks after the start of lambing in the lambs. Treatment group was found to have a significant effect on both ewe FEC (p<0.001) and lamb FEC (p = 0.001) with the group receiving the long-acting anthelmintic having the lowest ewe and lamb FECs. There was no significant effect on the DLWGs of the lambs. Pasture larval counts at the end of the study period were lowest in the long-acting wormer treatment group. The use of long-acting moxidectin may be helpful as part of a parasite control programme by reducing the worm burdens of ewes and their lambs, decreasing the number of anthelmintic treatments required in that year and by reducing pasture contamination for those sheep which will graze the pasture in the next year. However, like all anthelmintics, its use should be judicious to avoid selection for resistance.

Topics: Animal Husbandry; Animals; Anthelmintics; Farms; Feces; Female; Half-Life; Ivermectin; Larva; Macrolides; Nematoda; Nematode Infections; Parasite Egg Count; Postpartum Period; Pregnancy; Sheep; Sheep Diseases

A study was conducted to assess the effectiveness (fecal egg count reductions) and benefit (improvement in feed efficiency, average daily gain, health, and so forth) of a macrocyclic lactone (moxidectin [Cydectin Injectable] or doramectin [Dectomax 1% Injectable]) alone or in combination with a benzimidazole (oxfendazole [Synanthic Bovine Dewormer]) as used in steers upon their arrival at a feedlot. The cattle were kept in the feedlot for 181 days. Only minor differences in fecal egg count reductions were seen among treatments, with all egg counts reduced by more than 98% by 28 days posttreatment. Likewise, no statistically significant differences among treatments were seen in terms of animal performance (feed efficiency, intake, gain, morbidity, mortality, and carcass quality). All three treatment regimens appear to be comparable in decreasing nematode burdens and the consequences thereof in feedlot cattle.

Topics: Animals; Anthelmintics; Benzimidazoles; Cattle; Cattle Diseases; Drug Administration Schedule; Drug Therapy, Combination; Feces; Intestinal Diseases, Parasitic; Ivermectin; Macrolides; Meat; Parasite Egg Count; Southwestern United States; Treatment Outcome

This study evaluates the comparative serum disposition kinetics of injectable formulations of doramectin (DRM), ivermectin (IVM) and moxidectin (MXD) in Australian Merino sheep. Thirty-six, 2-year-old sheep were allocated by weight into six groups of six animals. Animals in each group received 200 microg/kg of DRM, MXD, IVM or a combination of two of these drugs by subcutaneous (s.c.) injection. Blood was collected at designated intervals (between 1 h and 40 days after treatment) and the serum analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that MXD administration produced a significantly higher maximum serum concentration and a more rapid absorption as compared with DRM and IVM. MXD and DRM had a significantly larger area under the concentration vs. time curve (AUC) than IVM, suggesting a more persistent effect for the former two products in sheep. The AUC for DRM was significantly higher when administered alone as compared with that observed when given in combination with MXD or IVM, suggesting preferential elimination of DRM compared with IVM and MXD from concurrent s.c. administration.

Topics: Animals; Area Under Curve; Injections, Subcutaneous; Insecticides; Ivermectin; Macrolides; Male; Sheep

To assess the efficacy of four macrocyclic lactones for the control of larvae of the Old World Screw-worm Fly (OWS), Chrysomya bezziana, and to examine the effects of excreted residues on the dung fauna.. 100 heifers were divided into five groups of 20 animals. One group remained untreated, whereas the other groups were treated respectively with pour-on formulations of moxidectin, eprinomectin or doramectin, or a sustained-release bolus of ivermectin.. At intervals of 1 to 15 weeks after treatment, five cattle from each group were challenged with newly-laid eggs of OWS. The efficacy of each treatment was determined 48 h later by comparing the number of myiases in the treated and untreated groups. Abundance of fly larvae in naturally-voided dung pads and the survival of a species of dung beetle, Onthophagus sagittarius, were used to assess the effects of drug residues on the dung fauna.. Moxidectin showed no activity against larvae of OWS during the first 14 days after treatment. Eprinomectin provided protection for 3 days after dosing, but failed at days 7 and 14, whereas doramectin was effective at day 7, but not at days 14 or 21. In contrast, no myiases were established on bolus-treated cattle from 14 to 102 days after treatment. Faecal residues of moxidectin had no effect on the survival of larvae of dung-feeding flies, whereas those of eprinomectin and doramectin reduced survival for 1 to 2 weeks. Dung voided by bolus-treated cattle inhibited fly breeding and had adverse effects on the development and survival of O sagittarius for up to 15 weeks after treatment.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Diptera; Drug Residues; Feces; Female; Insecticides; Ivermectin; Larva; Macrolides; Male; Myiasis

A field experiment and a controlled efficacy trial were conducted to demonstrate resistance of cattle trichostrongylid nematodes to endectocidal compounds in grazing cattle on the Humid Pampa, Argentina. Male Polled Hereford calves, aged 9-11 months old, with a history of frequent treatments with compounds of the avermectin/milbemycin class, were used for the trial. The field experiment involved six groups of 10 animals each, which were subcutaneously treated with either ivermectin (IVM), long-acting ivermectin (LA-IVM), moxidectin (MXD) or doramectin (DRM) at a dosage of 0.2mg/kg BW. A fifth group was treated orally with fenbendazole at a dosage of 5mg/kg BW; the sixth group of calves served as non-treated control. Faecal samples were collected from each animal on the day of treatment and at 14 days after treatment. Nematode egg counts were performed to estimate the faecal egg count reduction test (FECRT). The FECRT showed that reductions were 65% (IVM), -20% (LA-IVM) and 85% (DRM). Egg counts from calves treated with MXD or fenbendazole were reduced by 95 and 100%, respectively. For the controlled efficacy trial, six animals with the highest egg counts from the IVM, LA-IVM and non-treated control groups, were necropsied on day 18 after treatment to determine numbers and nematode species in the abomasum and small intestine. The results indicated that efficacy against Cooperia oncophora was 62.7 and 48% for IVM and LA-IVM, respectively. Neither of the IVM formulations showed efficacy against Trichostrongylus spp. in the small intestine. However, the absence of Trichostrongylus spp. in some animals of both treated and control groups precluded a valid assessment of efficacy or resistance. It was concluded that resistance of trichostrongylid nematodes to the avermectin/milbemycin class of compounds in grazing cattle of the Humid Pampa, Argentina, may be strongly established on farms where cattle are treated at frequent intervals throughout the year.

Topics: Animal Husbandry; Animals; Anthelmintics; Anti-Bacterial Agents; Argentina; Cattle; Cattle Diseases; Drug Resistance; Feces; Female; Fenbendazole; Ivermectin; Macrolides; Male; Trichostrongyloidea; Trichostrongyloidiasis

Topics: Animals; Anti-Bacterial Agents; Female; Injections, Intramuscular; Injections, Subcutaneous; Insecticides; Ivermectin; Macrolides; Mite Infestations; Sheep; Sheep Diseases; Time Factors; Treatment Outcome

Persistent anthelmintic efficacy of topical formulations (all at a dosage of 500 microg/kg) of doramectin (DOR), ivermectin (IVM), eprinomectin (EPR) and moxidectin (MOX), in comparison with untreated control cattle (CONT), was observed in stocker beef calves during a 112-day winter-spring grazing trial. Five groups of 15 calves per group were grazed on 15 separate 2 ha pastures following random assignment of animals to specific pastures and then to treatment groups. All of the 5 treatments were represented in each of the 15 pastures. All cattle were weighed on study Days 1, 0, 28, 56, 84, 111 and 112. Fecal samples for nematode egg counts were collected on Days 7, 0, at 7 day intervals through Day 56 and at 14 day intervals to Day 1 12. Pooled group fecal cultures for determining generic composition of nematode infections were prepared at 14 day intervals throughout the study. As based on fecal egg counts, anthelmintic activity of EPR and MOX was greater (p < 0.05) than values for IVM or CONT through Day 28. Activity of DOR was greater (p < 0.05) than that of IVM on Days 7 and 14 only. Although significance levels varied little among treated groups from Day 42 to the end of the study, egg counts and percent reduction values of EPR and MOX remained consistently lower numerically than egg counts and higher than reduction values respectively, of DOR and IVM through Day 70. From Day 70 on, IVM counts were numerically, but not significantly higher than values of CONT. Based on larval culture, Cooperia predominated from Day 0 through 28 and again from Days 70 to 98; Ostertagia was second in prevalence with highest percentages, which exceeded those of Cooperia, between Days 42 and 70. Bodyweights of all treated groups, with exception of IVM, were always significantly greater (p < 0.05) than weights of CONT. Weights of IVM were numerically greater, but not significantly greater than CONT only on Days 84 and 112. From Day 56 on, there were no significant differences between weights of DOR, EPR and MOX, however, numerical values for MOX were consistently higher than values for the other two. Final average total bodyweight gains were: 153.7 kg for MOX, 148.5 kg for EPR, 146.9 kg for DOR, 139.7 kg for IVM and 127.7 kg for CONT.

Topics: Administration, Topical; Animal Feed; Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Feces; Ivermectin; Macrolides; Nematode Infections; Parasite Egg Count; Poaceae; Weather

Two similar studies were conducted in New Zealand to compare the therapeutic and persistent activity of doramectin injectable, moxidectin pour-on, ivermectin pour-on and oxfendazole oral drench when administered to nematode-infected cattle which were then grazed on common pastures. On day 0 (treatment day), 40 cattle were weighed, faecal sampled and allocated on the basis of day--3 faecal egg counts (FEC) to four treatment groups. Cattle were then treated with either doramectin by subcutaneous (s.c.) injection, moxidectin and ivermectin by topical application, or oxfendazole orally using label-recommended dosages. Oxfendazole treatment served primarily as a control to monitor reinfection without persistent activity. Faecal samples for nematode egg counts and coprocultures for larval differentiation were collected six times between day 0 and day 56 and all cattle were reweighed on day 56. Doramectin reduced pretreatment FEC by 99.1% in the first study and by 100% in the second study when assessed at 14 days posttreatment. Corresponding reductions for moxidectin were 80.8% and 85.2%, for ivermectin 86.0% and 80% and oxfendazole 78.3% and 100%, respectively. Posttreatment rise in FEC indicated that reinfection of moxidectin-treated animals occurred at the same time as oxfendazole controls in both trials. Posttreatment rise in FEC with ivermectin pour-on was similar to moxidectin and oxfendazole in one study, but in the other study ivermectin pour-on delayed the rise by 14-21 days. The rise in FEC for doramectin was delayed for 14-21 days in one study and at least 21 days in the other. The better parasite control provided by doramectin resulted in greater weight gains for cattle over the 56-day period as compared to moxidectin pour-on, ivermectin pour-on and oxfendazole in both trials. Gains of doramectin treated cattle were significantly (p < 0.05) greater than those of ivermectin and moxidectin groups in one trial and the oxfendazole group only in the other.

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Feces; Female; Gastrointestinal Diseases; Injections, Subcutaneous; Ivermectin; Macrolides; Male; Nematode Infections; New Zealand; Parasite Egg Count; Recurrence; Weight Gain

Avermectins are effective agricultural pesticides and antiparasitic agents that are widely employed in the agricultural, veterinary and medical fields. The aim of this study was to investigate the inhibitory effects of selected avermectins including abamectin, doramectin, emamectin, eprinomectin, ivermectin and moxidectin that are used as drugs against a wide variety of internal and external mammalian parasites, on the carbonic anhydrase enzyme (CA, EC 4.2.1.1.) purified from fresh bovine erythrocyte. CA catalyses the rapid interconversion of carbon dioxide (CO2) and water (H2O) to bicarbonate ([Formula: see text]) and protons (H(+)) and regulate the acidity of the local tissues. Bovine erythrocyte CA (bCA) enzyme was purified by Sepharose-4B affinity chromatography with a yield of 21.96% and 262.7-fold purification. The inhibition results obtained from this study showed Ki values of 9.73, 17.39, 20.43, 13.39, 16.44 and 17.73 nM for abamectin, doramectin, emamectin, eprinomectin, ivermectin and moxidectin, respectively. However, acetazolamide, well-known clinically established CA inhibitor, possessed a Ki value of 27.68 nM.

Topics: Acetazolamide; Animals; Antiparasitic Agents; Carbonic Anhydrases; Cattle; Disaccharides; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Erythrocytes; Ivermectin; Macrolides; Molecular Structure

Gastrointestinal nematodes resistant to anthelmintics have been reported in several regions of Brazil, and they may be associated with economic losses for the cattle industry. This study aimed to evaluate the resistance status of gastrointestinal nematodes from naturally infected beef cattle to several commercially available anthelmintics, as well as to test the efficacy of combinations of anthelmintics against multi-resistant gastrointestinal nematodes. Ten farms located in Rio Grande do Sul state were selected by: farmers' consent; extensive raising system; availability of calves aged from 7 to 9 months naturally infected by gastrointestinal nematodes; absence of anthelmintic treatment for 60 days before the study; and presence of 70-100 calves or more of both genders with ≥ 200 eggs per gram of feces (EPG) (sensitivity of 50 EPG). These calves were distributed into 10 groups (of 7-10 animals) per farm and treated with ivermectin, doramectin, eprinomectin, fenbendazole, closantel, nitroxynil, disophenol, levamisole, albendazole, or moxidectin. Feces were collected 2 days before treatment and 14 days after treatment. Additional groups of 7-10 calves were used to test six different two-drug combinations at four of the studied farms. In general terms, fenbendazole was the most effective drug, followed by levamisole, disophenol, and moxidectin. However, parasite resistance to multiple drugs was found in all herds, especially in the genera Cooperia spp., Trichostrongylus spp., and Haemonchus spp.. Some of the two-drug combinations were effective against nematode populations identified as resistant to the same compounds when used as single drugs. The most effective combinations were moxidectin + levamisole, doramectin + fenbendazole, and levamisole + closantel. In this study, parasites resistant to the main commercially available anthelmintics were found in all herds, and some combinations of two active components belonging to different chemical groups were effective against multi-drug resistant gastrointestinal nematodes.

Topics: Albendazole; Animals; Animals, Domestic; Antinematodal Agents; Brazil; Cattle; Cattle Diseases; Drug Resistance, Multiple; Drug Therapy, Combination; Feces; Fenbendazole; Haemonchus; Intestinal Diseases, Parasitic; Intestines; Ivermectin; Levamisole; Macrolides; Nematoda; Nematode Infections; Parasite Egg Count; Red Meat; Salicylanilides

The present study therefore assessed the deleterious effects of MLs (ivermectin, abamectin, doramectin and moxidectin) on the reproductive parameters of engorged Rhipicephalus (Boophilus) microplus females that naturally detached from experimentally infested cattle in two experiments. The following reproductive parameters of engorged female ticks were analyzed: female weight, egg mass weight, percentage of hatchability, percentage of reduction in oviposition, percentage of reduction in hatchability, reproductive efficiency and percent control/efficacy of formulations with respect to reproductive parameters. In the experiment I, statistical analysis of the data grouped into 5-days intervals revealed that pour-on application of abamectin (500 mcg/kg) had significantly (p ≤ 0.05) reduced engorged female weight, egg mass weight and percent hatchability on days 6-15, 6-20 and 11-20 post-treatment (p. t.) compared to the respective data for detached and pre-selected engorged females in the control group. The abamectin, demonstrated 33.41% of reduction in oviposition, 6.77% in hatchability and abamectin efficacy was of 13.99%. In the experiment II, statistically significant reductions (p ≥ 0.05) were observed in animals treated subcutaneous with ivermectin (630 mcg/kg), doramectin (700 mcg/kg) and moxidectin (1000 mcg/kg) relative to the control for days 6-40, 6-48 and 6-40 p. t., respectively. Ivermectin reduced hatchability only on days 16-20 p. t., whereas doramectin significantly reduced (p ≤ 0.05) hatchability on days 6-10 and 16-35 p. t. For moxidectin, deleterious effects on hatchability were observed on days 16-35 p. t. The percent reductions in oviposition of engorged female ticks were 46.31%, 62.17% and 61.02% with ivermectin, doramectin and moxidectin treatments, respectively. The percent efficacy of the formulations on the reproductive parameters of engorged female ticks was 21.22% for ivermectin, 36.03% for doramectin and 35.45% for moxidectin. Among the MLs assessed, doramectin and moxidectin had the highest acaricidal efficacies and the most deleterious effects on the reproductive parameters of engorged R. (B.) microplus females. However, future studies will be necessary to assess the extent to which these effects, along with acaricidal activity, can be used to control the ectoparasite in cattle.

Topics: Acaricides; Animals; Cattle; Cattle Diseases; Female; Ivermectin; Macrolides; Oviposition; Random Allocation; Reproduction; Rhipicephalus; Tick Infestations

Certain dog breeds, especially Collies, are observed to exhibit neurotoxicity to avermectin drugs, which are P-glycoprotein (P-gp) substrates. This neurotoxicity is due to an ABCB1 gene mutation (ABCB1-1Δ) that results in non-functional P-gp expression. A developed Abcb1a knock-in/Abcb1b knock-out mouse model expressing the ABCB1-1Δ canine gene was previously reported and mice exhibited sensitivity upon ivermectin administration. Here, model and wild-type mice were administered P-gp substrates doramectin, moxidectin, and digoxin. While knock-in/knock-out mice exhibited ataxia, lethargy and tremor, wild-type mice remained unaffected. In addition, no neurotoxic clinical signs were observed in either mouse type administered domperidone, a P-gp substrate with no reported neurotoxicity in ABCB1-1Δ Collies. Overall, neurotoxic signs displayed by model mice closely paralleled those observed in ivermectin-sensitive Collies. This model can be used to identify toxic P-gp substrates with altered safety in dog populations and may reduce dog use in safety studies that are part of the drug approval process.

Topics: Animals; Anti-Infective Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Brain; Digoxin; Disease Models, Animal; Dog Diseases; Dogs; Domperidone; Female; Ivermectin; Macrolides; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutagenesis, Insertional

Topical formulations have achieved worldwide acceptance in veterinary medicine because their administration is an easy, less labor-intensive and nonstressing form. Any chemical compound that comes in contact with the skin has the potential to be locally and/or systemically absorbed. However, many factors related to the features of animal skin, composition of the topical formulation and to the drug itself can determine marked differences in the percutaneous absorption process. The aim of the current work was to characterize the pattern of in vitro percutaneous absorption for moxidectin (MXD) and doramectin (DRM), two of the most worldwide used topical macrocyclic lactone antiparasitic compounds in cattle. The work included the development of a simple and inexpensive in vitro assay useful to predict in vivo drug percutaneous absorption in cattle. Both drugs were administered as the commercial formulations intended for their topical administration to cattle. The in vitro studies were carried out using modified Franz-type vertical diffusion cells. Cattle skin slices of 500 μm thickness were prepared using a dermatome to separate the stratum corneum and upper epidermis from dermis and subcutaneous tissue. The receptor medium was sampled up to 72 h postadministration and drug concentrations were measured by HPLC. The parameters used to estimate the comparative in vitro skin permeation showed marked differences between DRM and MXD. A 5.29-fold longer lag time (T(lag)) was observed for DRM. Similarly, the flux (J) (2.93-fold) and the permeation coefficients (K(p) ) (2.95-fold) in cattle skin were significantly higher (P < 0.05) for DRM compared to those obtained for MXD. Additionally, the data obtained from the in vitro permeation studies was correlated with the plasma concentrations of both compounds achieved in vivo in cattle treated with the same topical formulations. Correlation coefficients between percentage of drug permeated in vitro vs. percentage of drug absorbed in vivo (up to 48 h post-treatment) were 0.856-0.887 (MXD) and 0.976-0.990 (DRM). However, the highest in vitro-in vivo correlations for both molecules were observed up to 24 h post-treatment A rapid screening method for testing different topical formulations can be achieved with the simple in vitro cattle skin permeation technique described here, which has been successfully adapted to test the comparative percutaneous absorption of MXD and DRM.

Topics: Administration, Topical; Animals; Biological Assay; Cattle; Insecticides; Ivermectin; Macrolides; Permeability; Skin Absorption

Four cattle parasiticides of the avermectin/milbemycin class were examined for lethal and sublethal effects on the zoophilic, African malaria vector Anopheles arabiensis. Ivermectin, moxidectin, doramectin, and eprinomectin were mixed with bovine blood and provided to laboratory-reared An. arabiensis in a membrane feeder. Ivermectin and eprinomectin were lethal to An. arabiensis at low concentrations (LC50s of 7.9 ppb and 8.5 ppb, respectively). While the lethality of doramectin (LC50 of 23.9 ppb), was less than that of ivermectin and eprinomectin, it markedly reduced egg development. The concentration of moxidectin required to reduce survivorship and egg production in An. arabiensis was > 100 fold greater than for ivermectin or eprinomectin. Moxidectin was weak in its actions against An. arabiensis relative to the other three chemicals. These results suggest that cattle treated with ivermectin or eprinomectin in the prescribed range of low dosages as parasiticides have blood toxic to zoophilic malaria vectors. Regionally coordinated, seasonal treatment of cattle could suppress An. arabiensis populations, thereby reducing malaria transmission. Doramectin (although less toxic) would have population level effects on egg production if used in this manner.

Topics: Animals; Anopheles; Cattle; Insect Vectors; Insecticides; Ivermectin; Lethal Dose 50; Macrolides; Mosquito Control

This study was conducted to investigate the efficacy of ivermectin (IVM), doramectin (DRM), and moxidectin (MXD) against Toxocara vitulorum in calves. In the study, 20 calves naturally infected with T. vitulorum were divided into four groups: three different treatment groups (n = 5) and one positive control (n = 5). The animals in each group received either IVM (Baymec®, Bayer), DRM (Dectomax®, Pfizer), or MXD (Cydectin®, Fort Dodge) by subcutaneous injection at a single dose of 0.2 mg/kg. Fecal egg counts were performed on all animals on days 0, 2, 4, 8, 12, and 16 post-treatment. In conclusion, IVM, DRM, and MXD significantly reduced the fecal egg counts on day 8 post-treatment (99.90%, 98.77%, and 99.57%, respectively). After the 12th day, IVM, DRM, and MXD were found to be 100% effective. There was no significant difference in efficacy between the three treatment groups at any of the sampling dates (P > 0.05). No side effects associated with nervous, respiratory, and gastrointestinal systems were observed. This is the first study to evaluate the comparative efficacy of subcutaneous administration of ivermectin, doramectin, and moxidectin against naturally infected T. vitulorum in calves.

Topics: Animals; Anthelmintics; Cattle; Cattle Diseases; Feces; Injections, Subcutaneous; Ivermectin; Macrolides; Parasite Egg Count; Toxocara; Toxocariasis; Turkey

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(1/2lambdaz)) 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.

Topics: Animals; Antiparasitic Agents; Area Under Curve; Chromatography, High Pressure Liquid; Female; Fluorescence; Half-Life; Injections, Subcutaneous; Ivermectin; Macrolides; Male; Rabbits

The aim of the present study was to carry out comparative therapeutic effect of moxidectin pour on, doramectin and ivermectin on psoroptes infestation in buffalo. A total of 318 buffalo in 77 small scale herds suspected to have mange mites were examined clinically and parasitologically. Fifty-three (16.66%) buffalo in 25 herds were recorded to be infested; 51 (16.35%) with psoroptic mites, and two (0.31%) with chorioptic mites. Buffalo with psoroptic mites were randomly allocated into three groups (17 buffalo each). First group was treated with moxidectin pour on at a dose rate of 0.5 mg kg(-1). The second group received doramectin (200 microg kg(-1) twice subcutaneously, 14 days apart). The third group received ivermectin (200 microg kg(-1) twice subcutaneously, 14 days apart). Adjunct to each drug, deltamethrin was applied to the surrounding environment twice at a two week interval. Treatment outcomes of 51 buffalo with psoroptic mites showed that moxidectin pour on and doramectin had a significant higher effect on mite count reduction (MANOVA, P < 0.01; Walks' Lambda, P < 0.01) and clinical sum scores (MANOVA, P < 0.05; Walks' Lambda, P < 0.05) compared with injectible ivermectin. On clinical level, the number of clinically recovered buffalo in moxidectin and doramectin treated groups was significantly (P < 0.05) higher than that of ivermectin treated group. The result of the present study indicated that psoroptic mites are the main cause of mange in buffalo in Lower Egypt. This is the first report that describes the effect of moxidectin in buffalo. Moxidectin is a good alternative and easily applied drug for treatment of psoroptes infestation in buffalo.

Topics: Analysis of Variance; Animals; Antiparasitic Agents; Buffaloes; Egypt; Ivermectin; Macrolides; Mite Infestations; Nitriles; Psoroptidae; Pyrethrins

Dung invertebrate colonization and degradation levels of faeces from cattle treated with endectocides were studied. Faeces of control and doramectin (DRM) (subcutaneous) and moxidectin (MXD) (subcutaneous and topical) treated animals were deposited on the field from 3 to 21 days post-treatment (pt). Pats were recovered after 6 to 42 days post-deposition (pd). Faecal weight, dry matter, arthropods number, and drugs concentrations were determined. Total arthropods number was higher in control (P<0.0001) than in the other groups from days 3 to 21 pt. Total number of insects recovered on days 3, 11, and 21 pt from control pats was significantly (P<0.001) higher than in treated-animal pats during all the trial. At day 21 pt, the insects' number in dung voided by DRM-treated cattle was (P<0.05) lower than in the other groups. Comparisons of dung degradation among treatments were inconclusive. A lower adverse effect was observed for MXD compared with DRM. No significant degradation of MXD or DRM was observed during the present trial.

Topics: Administration, Topical; Animals; Anthelmintics; Arthropods; Cattle; Cattle Diseases; Coleoptera; Diptera; Feces; Injections, Subcutaneous; Ivermectin; Macrolides; Male; Parasitic Diseases, Animal; Time Factors; Weather

The plasma kinetics of doramectin and moxidectin were evaluated in zebu Gobra under field conditions after subcutaneous administration of 0.2 mg kg(-1) of commercially available formulations for cattle. The results indicate that the absorption of moxidectin from the site of injection was significantly faster (absorption half-life [t1/2ab] = 0.7 day) than that of doramectin (t1/2ab = 3.1 days). Moxidectin peak plasma concentration (Cmax) was reached significantly earlier (tmax = 0.4 day) compared with that of doramectin (tmax = 5.3 days). No differences in Cmax values were observed; the area under the concentration-time curve was higher for doramectin (475 ng day ml(-1)) compared with moxidectin (198 ng day ml(-1)), while the mean residence time was longer for moxidectin (13.4 days) compared with doramectin (9.4 days). These results obtained give interesting information on doramectin and moxidectin pharmacokinetics in zebu Gobra, which show a similar pharmacokinetic profile as in other cattle.

Topics: Animals; Anthelmintics; Cattle; Female; Injections, Subcutaneous; Ivermectin; Macrolides

Derivatisation of the avermectines ivermectin (IVM), doramectin (DOR), abamectin (ABA) and eprinomectin (EPR), and the milbemycin moxidectin (MOX) to fluorescent derivatives is commonly used for quantitative analysis at relevant levels using high performance liquid chromatography (HPLC) with fluorescence detection. Problems associated with the differences in reactivity towards derivatisation (EPM) and limited stability of the derived products (IVM, DOR, ABA) may seriously hamper the applicability of the method and the reliability of the obtained results. A study was performed to obtain more insight in this derivatisation process from an organic chemistry point of view. This study demonstrated the occurrence of two main fluorescent derivatives: the trifluoroacetyl esters (flu-TFA) and the derivatives with a free hydroxy group at the glycosidic ring (flu-OH). Optimisation of the derivatisation conditions resulted in a fast and reproducible formation of the fluorescent derivatives for all analytes including EPM. The improved procedure involves the addition of 1-methylimidazole (MI), trifluoroacetic anhydride (TFAA), triethylamine (TEA) and trifluoroacetic acid (TFA) with a subsequent incubation for 30 min at 70 degrees C. With this procedure for IVM, DOR and ABA flu-TFA derivatives are obtained instead of flu-OH derivatives as generally described in literature. The derivatisation is reproducible in different milk samples and the derivatives proved to be stable for at least 80 h at room temperature. Using the optimised procedure a limit of detection (LoD) of 0.1 microg kg(-1) in milk was readily obtained.

Topics: Acetic Anhydrides; Animals; Cattle; Ethylamines; Fluoroacetates; Food Analysis; Imidazoles; Ivermectin; Macrolides; Milk; Trifluoroacetic Acid

A 3-year study was performed in southern Alberta, Canada to assess the effect of endectocide residues on the attractiveness of cattle dung to colonizing insects. In 2003 and 2004, insect captures were compared between pitfall traps baited with dung of untreated cattle and paired traps baited with dung of cattle that had been treated 7 days previously with topically applied doramectin, eprinomectin, ivermectin or moxidectin. Faecal residues associated with each compound affected insect captures in both spring and autumn of each year. Effects were detected (P < 0.05) for a total of 94 cases representing 27 insect taxa from 13 families in three orders (Coleoptera, Diptera, Hymenoptera). Two-fold differences in captures were common. Up to six-fold differences were observed. Eleven cases of attraction and 11 cases of repellency were associated with residues of doramectin. Eprinomectin tended to repel insects, with decreased captures for 19 of 29 cases of effect. Ivermectin showed a strong attractive effect, with increased captures for 17 of 25 cases. Moxidectin also showed a strong attractive effect, with increased captures for 17 of 18 cases. Comparisons between compounds suggested that results for doramectin best predicted results for eprinomectin and vice versa. In 2005, insect captures were compared between pitfall traps baited with dung of untreated cattle and traps baited with dung from cattle treated 3, 7 or 14 days previously with topically applied doramectin. Effects were detected in 14 cases plus one case of near significance (P= 0.053). Significant differences between control vs. days 3, 7 and/or 14 dung were detected in nine cases. Residues enhanced captures in seven of these cases. Day 14 dung affected captures in six of these cases. This study shows that endectocide residues can affect the number of insects attracted to colonize and oviposit in dung. Hence, the emergence of their offspring from field-colonized dung of untreated vs. endectocide-treated cattle should not be used as a measure of residue toxicity per se, but rather as a measure of 'insect activity'. Insect activity is a composite measure of residue toxicity, the number and species composition of insect colonists, and the mortality factors (e.g. predation, parasitism, competition) associated with the co-occurrence of these species in the dung pat.

Topics: Administration, Topical; Alberta; Animals; Cattle; Cattle Diseases; Ectoparasitic Infestations; Feces; Insecta; Insecticides; Ivermectin; Macrolides; Male; Oviposition; Pesticide Residues; Random Allocation; Time Factors

The development of anthelmintic resistance by nematode parasites is a growing problem for veterinarians and producers. The intensive use of the macrocyclic lactones for the treatment of a variety of parasitic diseases has hastened the development of resistance to this family of parasiticides among sheep, goats and cattle. As a result, resistance to ivermectin, moxidectin and doramectin by Haemonchus contortus has been documented throughout the world. While the exact sites of action of the macrocyclic lactones remain incompletely known, a critical point of entry for these drugs may be the terminally exposed sensory major neurons located in the cephalic end of the worms. These neurons, called amphidial neurons, are located in a pair of channels, the amphids, on either side of the pharynx and are exposed to the external environment via pores at the anterior tip of the worm. Through these neurons, important chemical and thermal cues are gathered by the parasite. Examination of serial electron micrographs of ivermectin-susceptible and ivermectin-resistant H. contortus allows for comparison of neuronal structure, arrangement of neurons within the amphidial channel, and distance of the tip of the dendritic processes to the amphidial pore. The latter of these characteristics provides a useful means by which to compare the association between the neurons and the external environment of the worm. Comparison of parental laboratory strains of ivermectin-susceptible H. contortus with related selected, ivermectin-resistant strains and with a wild-type ivermectin-susceptible field strain of H. contortus from Louisiana reveals that the ivermectin-resistant worms examined have markedly shorter sensory cilia than their ivermectin-susceptible parental counterparts. Additionally, the amphidial neurons of ivermectin-resistant worms are characterized by generalized degeneration and loss of detail, whereas other neurons outside of the channels, such as the labial and cephalic neurons, are normal in structure. Similar degeneration was also observed in field strains of doramectin-resistant H. contortus collected from a New Jersey alpaca heard. These findings raise a number of questions regarding the relationship between amphidial structure and macrocyclic lactone resistance as well as the role of amphids as a means of entry for these molecules. While shortened amphidial sensilla are associated with ivermectin resistance, it remains unclear if such a structural modification facili

Topics: Animal Structures; Animals; Anthelmintics; Cilia; Drug Resistance, Multiple; Haemonchus; Ivermectin; Larva; Macrolides; Neurons; Sense Organs; Species Specificity

Self-licking behaviour in cattle has recently been identified as a determinant of the kinetic disposition of topically-administered ivermectin. In the present study, we document the occurrence and extent of transfer between cattle of three topically-administered endectocides, as a consequence of allo-licking. Four groups of two Holstein cows each received one pour-on formulation of doramectin, ivermectin, or moxidectin, or no treatment. The cows were then kept together in a paddock. Systemic exposure to each topically-administered endectocide was observed in at least five of six non-treated cattle. Plasma and faecal drug concentration profiles in non-treated animals were highly variable between animals and within an animal, and sometimes attained those observed in treated animals. Drug exchanges were quantified by measuring plasma and faecal clearances after simultaneous i.v. administration of the three drugs as a cocktail. Plasma clearances were 185+/-43, 347+/-77 and 636+/-130ml/kg/day, faecal clearances representing 75+/-26, 28+/-13, and 39+/-30% of the plasma clearance for doramectin, ivermectin and moxidectin, respectively. The amount of drug ingested by non-treated cattle attained 1.3-21.3% (doramectin), 1.3-16.1% (ivermectin), 2.4-10.6% (moxidectin) of a pour-on dose (500 microg/kg). The total amount of drug ingested by all non-treated cattle represented 29% (doramectin), 19% (ivermectin), and 8.6% (moxidectin) of the total amount of each drug poured on the backs of treated animals. The cumulative amounts of endectocide ingested by each non-treated cow ranged from 1.3 to 27.4% of a pour-on dose. Oral bioavailability after drug ingestion due to allo-licking was 13.5+/-9.4, 17.5+/-3.5 and 26.1+/-11.1% for doramectin, ivermectin and moxidectin, respectively. The extent of drug exchange demonstrated here raises concerns for drug efficacy and safety, emergence of drug resistance, presence of unexpectedly high residue levels in treated and/or untreated animals and high environmental burdens. Moreover, scientific and regulatory aspects of clinical and bioequivalence trials for topical drug administration in cattle should be explored.

Topics: Administration, Oral; Administration, Topical; Animals; Behavior, Animal; Biological Availability; Cattle; Dose-Response Relationship, Drug; Drug Combinations; Feces; Injections, Intravenous; Insecticides; Ivermectin; Macrolides

Bioassays were conducted to study the effect of a single therapeutic dose of injectable ivermectin, doramectin or moxidectin given to cattle and pigs and excreted in their faeces, against larvae of the housefly, Musca domestica L. (Diptera: Muscidae). Five cattle were treated with each of the test products. Cattle faecal samples were collected before treatment and on days 1, 2, 3, 6, 10, 16, 20, 23 and 28 after treatment. Three groups of pigs, each comprising 12-14 pregnant sows and gilts, were used in the experiment. Pig faeces was collected from each group before treatment and on days 1, 3, 5, 7, 9, 11, 13, 15 and 20 after treatment. Thirty, first-stage larvae were placed into 100 g of faeces. Five replicates were examined for each time-point and for each endectocide group. Evaluation was based on the number of larvae surviving to adult emergence. Low numbers of adults emerged from samples taken from cattle 1 day after treatment, indicating that ivermectin and doramectin were rapidly excreted in the faeces and affected the development of the house fly. A larvicidal effect of both drugs in cattle faeces was present for a period of about 3-4 weeks and lasted a few days longer in cattle treated with doramectin than with ivermectin. In cattle, the larvicidal activity of moxidectin was first observed in faecal samples collected 2 days post-treatment; however, it killed fewer larvae than the other two drugs. The larvicidal effect of moxidectin subsequently decreased. Ivermectin and doramectin exhibited a pronounced larvicidal effect against the house fly in the faeces of pigs. The effect of doramectin was of longer duration. Moxidectin gave the weakest larvicidal effect in pig faeces. The main difference between the results obtained for the two livestock species is that peak toxicity occurred relatively later and for a shorter duration in pig than in cattle faeces.

Topics: Animals; Cattle; Cattle Diseases; Ectoparasitic Infestations; Feces; Houseflies; Insecticides; Ivermectin; Larva; Macrolides; Swine; Swine Diseases

Anthelmintic products form the basis of helminth control practices on horse stud farms at present. Regular evaluation of the efficacy of these products is advisable, as it will provide information on the worm egg reappearance period and the resistance status in the worm population. The aim of this study was to evaluate the efficacy of doramectin, pyrantel pamoate, ivermectin and moxidectin on a Thoroughbred stud farm in the Western Cape Province, South Africa. The study also compared the anthelmintic efficacy of two moxidectin formulations administered at their recommended dosages (an injectable, at 0.2 mg/kg, not registered for horses, and an oral gel at 0.4 mg/kg, registered for horses). Two mixed-sex groups of 30 yearlings and 40 weaners were tested in 2001 and 2002, respectively, divided into 3 and 4 groups of equal size. In 2001, moxidectin was one of 3 drugs administered orally and at a dose rate of 0.4 mg/kg. In 2002, pyrantel pamoate and ivermectin were orally administered at 19 and 0.2 mg/kg. Moxidectin and doramectin (the latter not registered for horses) were administered by intramuscular injection at a dose of 0.2 mg/kg, the dosage registered for other host species. The faecal egg count reduction test was used to determine the anthelmintic efficacies in both years. Each animal acted as its own control and the arithmetic mean faecal egg count and lower 95% confidence limit was calculated for each of the groups. A 100% reduction in the faecal egg counts and a 100% lower 95% confidence limit was recorded for moxidectin (0.4 mg/kg) in 2001. In 2002, a 99% and 96% reduction was recorded for pyrantel pamoate and ivermectin, respectively. In the same year doramectin and moxidectin (both injectable and given at 0.2 mg/kg) did not have any effect on worm egg counts. Of the 4 drugs tested in 2002, only pyrantel pamoate recorded lower 95% confidence limits above 90%.

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Feces; Female; Fenbendazole; Helminthiasis, Animal; Horse Diseases; Horses; Injections, Intramuscular; Ivermectin; Macrolides; Male; Parasite Egg Count; Pyrantel Pamoate; Random Allocation; Treatment Outcome

Pour-on formulations of four endectocide products were compared to assess the effect of faecal residues on insects developing in naturally-colonized dung of treated cattle. In each of three independent experiments, suppression of insects was associated with application of doramectin, eprinomectin and ivermectin, but no effect was observed for moxidectin. When data were combined across experiments to increase sample sizes, suppression of insects was observed for each compound, with the least effect being observed for moxidectin. Based on the number of species affected and duration of suppression, doramectin > ivermectin > eprinomectin >> moxidectin were ranked in descending order of adverse effect. A second set of three independent experiments was performed to assess the effect of endectocide treatment on dung degradation. Delayed degradation was observed for dung of cattle treated with doramectin, eprinomectin and moxidectin in the first experiment. No effect of treatment was detected in the second experiment. An effect of moxidectin was detected in the third experiment, but differences could not be detected with subsequent post-hoc tests. When data were combined across experiments to increase sample sizes, delayed degradation was detected only for eprinomectin. The apparent discrepancy between the low effect of moxidectin on insects versus its effect of dung degradation suggests the confounding action of other unidentified factors. Results of the current study indicate that use of moxidectin is least likely to affect the natural assemblage of insects associated with cattle dung.

Topics: Analysis of Variance; Animals; Cattle; Feces; Insecta; Insecticides; Ivermectin; Larva; Macrolides

Duplicate studies in France and Northern Ireland were carried out to determine the persistent efficacy of topical moxidectin and doramectin against natural infections of Cooperia oncophora. In each study, groups of 15 nematode-naïve calves were treated either with topical doramectin or moxidectin, and put out to graze on pasture contaminated with C. oncophora infective larvae. The persistent efficacy for preventing establishment of infection was assessed by the time to faecal egg excretion of C. oncophora eggs. It was found that the moxidectin treatment prevented infection for less than 10 days and the effect of doramectin lasted for 24 days.

Topics: Administration, Topical; Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Feces; France; Ivermectin; Macrolides; Male; Northern Ireland; Parasite Egg Count; Random Allocation; Trichostrongyloidea; Trichostrongyloidiasis

Cattle were treated with topical formulations of endectocides to assess the larvicidal activity of faecal residues against horn fly, Haematobia irritans (L.), house fly, Musca domestica L., and stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae). In laboratory bioassays, doramectin, eprinomectin and ivermectin suppressed horn fly in dung of cattle treated at least 4 weeks previously and suppressed house fly and stable fly in dung of cattle treated 1-5 weeks previously. Moxidectin suppressed horn fly in dung from cattle treated no more than one week previously and did not suppress house fly and stable fly. Results combined for the three species across two experiments suggested that, ranked in descending order of larvicidal activity, doramectin > ivermectin approximately = eprinomectin >> moxidectin.

Topics: Animals; Anti-Bacterial Agents; Antinematodal Agents; Cattle; Cattle Diseases; Diptera; Ectoparasitic Infestations; Feces; Insecticides; Ivermectin; Larva; Macrolides; Nematode Infections

The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) were obtained at (tmax) 7.9 h (IVM), 8 h (DRM) and 7.9 h (MXD). The area under the concentration time curve (AUC) of MXD (92.8 ng x day/ml) was significantly larger than that of IVM (46.1 ng x day/ml) but not of DRM (53.3 ng x day/ml) and mean residence time of MXD (17.5 days) was significantly longer than that of either avermectin, while that of DRM (3 days) was significantly longer than that of IVM (2:3 days). The highest (dry weight) faecal concentrations (IVM: 19.5 microg/g; DRM: 20.5 microg/g; MXD: 16.6 microg/g) were detected at 24 h for all molecules and each compound was detected (> or = 0.05 microg/g) in faeces between 8 h and 8 days following administration. The avermectins and milbemycin with longer residence times may have extended prophylactic activity in horses and may be more effective against emerging and maturing cyathostomes during therapy. This will be dependent upon the relative potency of the drugs and should be confirmed in efficacy studies.

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Area Under Curve; Chromatography, High Pressure Liquid; Feces; Horse Diseases; Horses; Ivermectin; Macrolides; Parasitic Diseases, Animal; Treatment Outcome

The milk kinetics of doramectin after a single subcutaneous administration and moxidectin following a single subcutaneous or oral drench were studied in goats (n = 15) at a dosage of 0.2 mg kg(-1). Doramectin could be detected in the milk for 21.0+/-2.9 days after subcutaneous treatment, and the total fraction of the dose recovered from the milk was estimated to be 2.9+/-0.88 per cent. Moxidectin, after either oral or subcutaneous administration, could be detected in the milk up to day 40 and the total fractions of the dose recovered from the milk were estimated to be 5.7+/-1.04 per cent and 22.53+/-1.09 per cent, respectively. The mean residence time after subcutaneous administration indicated that moxidectin delivered by the milk persists three times longer than doramectin; furthermore, the total fraction of the dose of moxidectin recovered from the milk was 7.7 times higher than that of doramectin.

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Area Under Curve; Female; Goats; Half-Life; Injections, Subcutaneous; Ivermectin; Lactation; Macrolides; Milk; Statistics, Nonparametric

In this study, the effect of doramectin, moxidectin and netobimin was investigated in naturally infected Syphacia muris in rats. The natural infection was determined by the use of cellophane tape method on the perianal region and by the technique of centrifugal flotation of feces. The infected rats were divided into three treated and one control group (N = 10). Doramectin and moxidectin at the dose of 0.2 mg/kg per day and netobimin at the dose of 7.5 mg/kg per day were given in the diet for 4 days. Cellophane tape preparations were performed in all groups on 4th and 7th day after the last treatment. The rats of treated groups were necropsied on 7th day after the last treatment together with that of control group. While doramectin and netobimin were highly effective against S. muris, moxidectin was not found to be effective for eradication of S. muris.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Cellophane; Female; Guanidines; Ivermectin; Macrolides; Male; Oxyuriasis; Oxyuroidea; Perianal Glands; Random Allocation; Rats; Rats, Sprague-Dawley; Rodent Diseases

Treatment methods in the last century involved the use of substances such as sulphur, mercury, hellebore, arsenic, nicotine and others, applied in various ways. The advent of dips in 1843 signalled an advance. However, the biology of the mite, Psoroptes ovis, the epidemiology of sheep scab and the lack of persistence of the acaricides necessitated repeated laborious treatments to ensure success. In 1947 this changed with the use of organo chlorines (OCs) which had up to 3 months residual activity. The use of OCs led to the eradication of psoroptic mange of sheep in USA. Organo phosphates (OPs) were introduced in the late fifties and synthetic pyrethroids (SPs) in the early seventies. In 1985, due to sheep tissue residues, lindane (OC) was withdrawn from the market and this greatly reduced the capacity for effective sheep scab control. Before the arrival of the endectocidal avermectin, ivermectin in 1978 and its successful use as an acaricide in 1992, control of psoroptic mange was limited to plunge dipping. In 1994 moxidectin, a milbemycin, was found to be effective and to have the added benefit of at least 4 weeks persistent activity. Another avermectin doramectin was shown, in 1995, to successfully treat scab and recently an ivermectin bolus has been introduced which has a 100 days' activity and is fully therapeutic and prophylactic. Strict attention to detail in the use of injectable products is essential in order to achieve satisfactory results. Work is progressing on the use insect growth regulators (IGRs) and also on naturally occurring substances such as linalool, neem and lavender oil. At the CVRL Dublin, promising results have been achieved with neem and some IGRs. Other areas of interest are allemones, synergists, microclimate manipulation, sheep breed resistance and vaccines. Successful control depends on epidemiological knowledge, accurate diagnostic techniques, intimate knowledge of the mite's life cycle, its behaviour on and off the host, its macro and molecular biology, the nature of the pathogenesis of the disease, sheep husbandry practices, nutritional and environmental factors; also farmer awareness and attitudes. The variable responses of sheep to the mite, the unpredictable incubation period, course, manifestations and outcome make this an intriguing and perplexing disease. Ways to overcome these problems and to achieve possible eradication are discussed.

Topics: Acyclic Monoterpenes; Animals; Anti-Bacterial Agents; Disease Outbreaks; History, 19th Century; History, 20th Century; Injections, Subcutaneous; Insecticides; Ivermectin; Juvenile Hormones; Macrolides; Mite Infestations; Mites; Monoterpenes; Sheep; Sheep Diseases; Terpenes; United Kingdom

The pharmacokinetic behaviour of doramectin after a single subcutaneous administration and moxidectin following a single subcutaneous or oral drench were studied in goats at a dosage of 0.2 mg kg(-1). The drug plasma concentration-time data were analysed by compartmental pharmacokinetics and non-compartmental methods. Maximum plasma concentrations of moxidectin were attained earlier and to a greater extent than doramectin (shorter t(max) and greater C(max) and AUC than doramectin). MRT of doramectin (4.91 +/- 0.07 days) was also significantly shorter than that of moxidectin (12.43 +/- 1.28 days). Then, the exposure of animals to doramectin in comparison with moxidectin was significantly shorter. The apparent absorption rate of moxidectin was not significantly different after oral and subcutaneous administration but the extent of absorption, reflected in the peak concentration (C(max)) and the area under the concentration-time curve (AUC), of the subcutaneous injection (24.27 +/- 1.99 ng ml(-1) and 136.72 +/- 7.35 ng d ml(-1) respectively) was significantly greater than that of the oral administration (15.53 +/- 1.27 ng ml(-1) and 36.72 +/- 4.05 ng d ml(-1) respectively). The mean residence time (MRT) of moxidectin didn't differ significantly when administered orally or subcutaneously. Therefore low oral bioavailability and the early emergence of resistance in this minor species may be related. These results deserve to be correlated with efficacy studies for refining dosage requirements of endectocides in this species.

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Female; Goats; Injections, Subcutaneous; Ivermectin; Macrolides

The persistence of the broad-spectrum antiparasitic activity of endectocide compounds relies on their disposition kinetics and pattern of plasma/tissues exchange in the host. This study evaluates the comparative plasma disposition kinetics of ivermectin (IVM), moxidectin (MXD) and doramectin (DRM) in cattle treated with commercially available injectable formulations. Twelve (12) parasite-free male Hereford calves (180-210 kg) grazing on pasture were allocated into three groups of four animals each. Animals in each group received either IVM (Ivomec 1%, MSD AGVET, Rahway, NJ, USA), MXD (Cydectin 1%. American Cyanamid, Wayne, NJ, USA) or DRM (Dectomax 1%, Pfizer Inc., New York, NY, USA) by subcutaneous injection at a dose of 200 micrograms/kg. Jugular blood samples were collected from 1 h up to 80 days post-treatment, and plasma extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The parent molecules were detected in plasma between 1 h and either 70 (DRM) or 80 (IVM and MXD) days post-treatment. The absorption of MXD from the site of injection was significantly faster (absorption half-life (t1/2ab) = 1.32 h) than those of IVM (t1/2ab = 39.2 h) and DRM (t1/2ab = 56.4 h). MXD peak plasma concentration (Cmax) was reached significantly earlier (8.00 h) compared to those of IVM and DRM (4-6 days post-treatment). There were no differences on Cmax values: the area under the concentration-time curve (AUC) was higher for IVM (459 ng.d/mL) and DRM (627 ng.d/mL) compared to that of MXD (217 ng.d/mL). The mean plasma residence time was longer for MXD (14.6 d) compared to IVM (7.35 d) and DRM (9.09 d). Unidentified metabolites were detected in plasma: they accounted for 5.75% (DRM), 8.50% (IVM) and 13.8% (MXD) of the total amount of their respective parent drugs recovered in plasma. The comparative plasma disposition kinetics of IVM, MXD and DRM in cattle, characterized over 80 days post-treatment under standardized experimental conditions, is reported for the first time.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Chromatography, High Pressure Liquid; Ivermectin; Macrolides; Male

The persistent efficacy of four commercially available macrocyclic lactones (ML) in maintaining reduced faecal egg counts in cattle grazing naturally infested pastures was evaluated in 44 zebu animals aged 1-2 years in Zambia. The study started in February (rainy season) when the strongyle egg output was increasing. Four days before the start of the trial, all animals were treated with a double dose of oxfendazole. They were then divided into five groups which were again treated on day 0. Groups A, D, I and M received 0.2 mg kg-1 of abamectin, doramectin, ivermectin and moxidectin, respectively. Animals of group C received albendazole (7.5 mg kg-1). Faecal samples were collected twice a week for egg counts and larval differentiation. Faecal egg counts in the C group increased from day 21 onwards and plateaued from day 42 between 180 and 380 eggs per gram. The main genera found in cultures were Cooperia (90%) and Haemonchus (7%). Faecal egg excretion in groups M, A, D and I started on day 35, 42, 42 and 45, respectively. Subsequently and until day 84, average counts in these four groups were always significantly lower than in group C. Compared with albendazole, all four ML gave over 95% reduction in cumulative faecal egg counts for 42 days after treatment. The percentage efficacy was still over 84% by day 84 when an average cumulative egg count of 11320 eggs per gram faeces was calculated in group C. In addition, there was no significant difference in efficacy between the four ML groups at any of the sampling dates. During the trial no significant difference in weight gain between any of the groups was observed.

Topics: Animals; Anti-Bacterial Agents; Antinematodal Agents; Cattle; Cattle Diseases; Feces; Haemonchiasis; Haemonchus; Ivermectin; Macrolides; Nematode Infections; Parasite Egg Count; Zambia

The persistent efficacy of some anthelmintics brings advantages in nematode control in domestic animals. However, scientific assessment of persistent efficacy is relatively new, and a feature of published data has been variability in the reported endpoint for this activity. Trial design and method of calculating efficacy have a large bearing on the results obtained. Three types of studies used to evaluate the persistent efficacy of anthelmintics are briefly discussed and compared. In the first type of study, animals are treated followed by a single infection at 7, 14 or more days after treatment. The reduction in worm counts compared to an untreated control group gives a good indication of the persistent efficacy of the product at each time point. One control group can be used for several time points. In the second type of study, the animals are treated and then infected daily from day 1 until 7 days, 14 days or longer after treatment. The animals are slaughtered approximately 3 weeks after the last infection. This approach may better mimic a natural infection but the results obtained are an average reduction over the whole infection period. At the end of the evaluated period, the actual protection may be considerably lower than the average. From this test, it is difficult to define when the protection decreases or disappears. In this test, a control group is required for each period. In the third type of study, a modification of the second, the animals are treated and infected as before but animals are slaughtered soon (2-5 days) after the last infection. Based on the reduction of, for example, the different Ostertagia stages a more specific determination of the persistent efficacy 0-3 days (L3), 3-7 (EL4), 7-14 (LL4 + EL5) and more than 14 days (LL5 + adults) before slaughter can be obtained. Only two groups of animals are required to cover a 3 week period and the average efficacies can be reduced to about one week.

Topics: Animals; Animals, Domestic; Anthelmintics; Anti-Bacterial Agents; Clinical Protocols; Ivermectin; Macrolides; Nematoda; Nematode Infections; Ostertagiasis; Reproducibility of Results; Research Design

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Feces; Female; Haemonchus; Ivermectin; Macrolides; Male; Nematode Infections; Oesophagostomum; Parasite Egg Count; Random Allocation; Trichostrongylus

Topics: Animal Feed; Animals; Animals, Domestic; Anti-Bacterial Agents; Anti-Infective Agents; Benzimidazoles; Cephalosporins; Chlortetracycline; Drug Residues; Fenbendazole; Food Additives; Food Analysis; Guanidines; Ivermectin; Macrolides; Nitriles; Oxytetracycline; Tetracycline; Triazines; Veterinary Medicine

The avermectins ivermectin and doramectin and the milbemycins milbemycin A4 oxime and moxidectin were tested for filaricidal activity in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi, and B. pahangi. Single subcutaneous doses of 0.005-5 mg/kg (L. carinii), 0.0005-0.5 mg/kg (A. viteae), 0.5 and 5 mg/kg (B. malayi), and 5 mg/kg (B. pahangi) were injected. Necropsies were performed 42 days after treatment. The avermectins caused a strong and rapid reduction of microfilaraemia in L. carinii and A. viteae infections within a few hours after treatment but showed only moderate efficacies on microfilariae of Brugia spp. The effects of the milbemycin derivatives on L. carinii and A. viteae microfilariae were generally weaker than those of the avermectins. However, moxidectin was comparatively active against microfilariae of Brugia spp. Subsequently the parasitaemia levels of L. carinii and A. viteae infected animals remained either almost completely depressed or tended to reincrease in a dose dependent manner whereas there was generally a continuous decrease of microfilaraemia levels in Brugia spp. infected animals. Adulticidal effects were limited to A. viteae although with neither dose of neither drug > 95% reductions of adult worm counts were reached. However, pathogenic influences of the drugs were observed on intrauterine embryonic stages of the parasites.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Brugia; Dipetalonema; Dose-Response Relationship, Drug; Female; Filariasis; Filarioidea; Ivermectin; Macrolides; Male; Microfilariae; Muridae; Parasitemia; Recurrence