Efficacy of topically administered doramectin against eyeworms, lungworms, and gastrointestinal nematodes of cattle.

OBJECTIVE: To evaluate efficacy of topically administered doramectin against eyeworms, lungworms, and gastrointestinal nematodes of cattle. ANIMALS: 400 cattle (20 cattle in each of 20 trials). PROCEDURE: Trials were conducted in North America; natural and experimentally induced infections were used. In each trial, cattle were allocated randomly to control (placebo [saline [0.9% NaCl] solution at 1 ml/10 kg of body weight] or untreated; n = 10) or doramectin-treated (500 microg/kg of body weight; 10) groups. Treatments were applied in a single passage along the midline of the back, from the withers to the tailhead. Cattle were euthanatized > or =14 days after treatment, and worm burdens were determined by use of standard techniques. RESULTS: Efficacy of doramectin was > or =95.3% against adults of Thelazia gulosa, T skrjabini, Dictyocaulus viviparus, Haemonchus contortus, H placei, Ostertagia lyrata, O ostertagi, Trichostrongylus axei, Bunostomum phlebotomum, Capillaria spp, Cooperia oncophora, C pectinata, C punctata, C spatulata, C surnabada, Nematodirus spathiger, Strongyloides papillosus, T colubriformis, Oesophagostomum radiatum, and Trichuris spp. Efficacy was 95.1% against fourth-stage larvae of D viviparus, H placei, O lyrata, O ostertagi, T axei, C oncophora, C punctata, C spatulata, C surnabada, N helvetianus, T colubriformis, O radiatum, and Trichuris spp. In addition, efficacy against inhibited fourth-stage larvae of O ostertagi and Ostertagia spp was > or =98.1%. CONCLUSIONS AND CLINICAL RELEVANCE: A single topical application of doramectin pour-on was efficacious against a broad range of nematode species in cattle.

Efficacy of a pour-on formulation of doramectin against lice, mites, and grubs of cattle.

OBJECTIVE: To determine effectiveness of a pour-on formulation of doramectin against Damalinia bovis, Haematopinus eurysternus, Linognathus vituli, Solenopotes capillatus, Chorioptes bovis, Sarcoptes scabiei, Hypoderma bovis, and Hypoderma lineatum. ANIMALS: Cattle of various ages with naturally acquired or artificial infestations with 1 or more species of lice, mites, or grubs. PROCEDURE: In 10 louse and 6 mite studies, cattle were treated with doramectin (500 microg/kg, topically) on day 0, and parasite counts were performed approximately weekly from days 0 to 35. In 6 grub studies, cattle expected to harbor Hypoderma spp were treated before emergence of warbles. After warbles began to emerge, they were counted every 2 weeks, and grubs were collected and identified by species. RESULTS: Burdens of D bovis, H eurystemus, L vituli, and S capillatus on doramectin-treated cattle were 0 by 28 days after treatment. Burdens of C bovis and S scabiei decreased to 0 in naturally infested cattle and approximately 0 in artificially infested cattle by day 14 to 15. In grub studies, 107 of 136 control cattle had warbles, whereas 2 of 136 doramectin-treated cattle had 1 warble each, which represented a cure rate of 98.5%. CONCLUSION AND CLINICAL RELEVANCE: One topical application of doramectin was highly efficacious against common species of lice, mites, and grubs known to affect performance, health, and appearance of cattle.

Field efficacy of doramectin pour-on against naturally-acquired, gastrointestinal nematodes of cattle in North America.

Seven studies were conducted under field conditions in North America to evaluate the therapeutic efficacy of doramectin in a pour-on formulation at a dosage of 500 microg/kg (1 ml/10 kg) for cattle harboring naturally-acquired infections of gastrointestinal nematodes, including species of Haemonchus, Ostertagia, Trichostrongylus, Bunostomum, Cooperia, and Oesophagostomum. In each study, 40 to 100 cattle were randomly allocated to a saline- or doramectin-treated group in a tiered manner based on Day -7 bodyweight. On Day 0, the cattle received either saline or doramectin topically, according to their treatment group. Weather and safety observations were made following treatment. No adverse reaction to treatment was observed at any time during these studies. Fecal egg count (FEC) determinations were carried out on each animal on Days -7, 0, 7, 14, and 21. Reductions in FEC for the doramectin-treated animals compared to saline-treated cattle were > or = 96.0% by Day -7 and > or = 99.0% on Days 14 and 21 for each study. Across all studies regardless of weather conditions, the reduction by Day 21 for the doramectin-treated animals compared to saline controls was 99.7% (p < or = 0.0001) and compared to pretreatment levels in doramectin-treated cattle was 99.9% (p < or = 0.0001). Doramectin pour-on should provide a useful new treatment for controlling nematode parasites of cattle.

Persistent efficacy of doramectin against experimental challenge with Ostertagia ostertagi in cattle.

Two studies were conducted in North America to evaluate the persistent efficacy of doramectin injectable solution against experimental challenge with infective larvae of Ostertagia ostertagi. In both studies, four groups of 10 randomly-assigned calves, negative for trichostrongyle-type eggs on fecal examination, were treated subcutaneously in the midline of the neck with saline (1 ml 50 kg-1) on Day 0 or doramectin (200 micrograms kg-1 = 1 ml 50 kg-1) on Day 0, 7, or 14. Two additional calves from the same pool of animals were randomly assigned as larval-viability monitors and received no treatment. Beginning on Day 14 and continuing through Day 28, the 40 treated calves each were given approximately 1000 infective larvae of O. ostertagi by gavage daily; the two larval-viability monitors were inoculated in a similar manner with approximately 30,000 larvae as a single dose on Day 28. Animals were slaughtered on Day 42 in one study and on Days 42, 43, or 46 in the second. The abomasum from each calf was harvested and processed for worm recovery. A 2% aliquot of abomasal contents plus wash was examined for worm quantification and identification. Geometric mean O. ostertagi burdens were calculated from the log (O. ostertagi count + 1) and were used to estimate percentage reduction. In both studies, doramectin injectable solution was > or = 99.6% efficacious in reducing infection resulting from challenge with infective larvae of O. ostertagi for at least 21 days posttreatment; by 28 days posttreatment, efficacy was 87.3% in one study and 99.7% in the other.

Efficacy of doramectin for treatment of experimentally induced infection with gastrointestinal nematodes in calves.

OBJECTIVE: To determine the efficacy of injectable doramectin against experimentally induced infections with adult and larval (L4) stages of gastrointestinal nematodes in calves. PROCEDURES: In each experiment, between 20 (experiments 1 and 2) and 30 (experiment 3) parasite-free yearling calves were selected and allotted to groups of 10/group. All calves received oral inoculation of the following infective larval stages of these nematode species: Cooperia onchophora, C punctata, C zurnabada, Cooperia spp, Haemonchus placei, Nematodirus helvetianus, Oesophagostomum radiatum, Ostertagia ostertagi, Trichostrongylus axei, and T colubriformis. Infections or treatments were timed so that, by day of treatment, the population of each parasite species had matured to the stage to be tested (adult or L4). On day of treatment, calves received doramectin (200 micrograms/kg of body weight, SC), and infected nonmedicated control calves received saline solution SC at the same time. All calves were slaughtered at least 14 days after treatment. RESULTS: Efficacy against the following adult and L4 species was > or = 99%: C onchophora, C punctata, C zurnabada, Cooperia spp, H placei, Oes radiatum, O ostertagi, and T colubriformis. Doramectin was also 100% efficacious against the L4 stage of T axei. Efficacy against the adult and L4 stages of N helvetianus was 9.6 and 77.4 to 83.3%, respectively. CONCLUSIONS: Doramectin, at a dosage of 200 micrograms/kg, is effective in controlling the prevalent gastrointestinal nematodes (adult and L4 stages) found in naturally infected calves. CLINICAL RELEVANCE: Doramectin, a new anthelmintic, was effective against recent field strains of the most prevalent gastrointestinal parasites found in cattle in the United States, and could provide another alternative for control of these parasites.

Activity of doramectin against nematode and arthropod parasites of swine.

The efficacy of doramectin, a novel avermectin, was assessed against both naturally-acquired and experimentally-induced infections of gastrointestinal roundworms, lungworms, kidneyworms, lice and mites in studies conducted across North America and Europe. Twenty-two studies evaluated efficacy against fourth larval and adult stages of the following nematode species: Hyostrongylus rubidus, Ascaris suum, Strongyloides ransomi, Oesophagostomum dentatum, Oesophagostomum quadrispinulatum, Trichuris suis, Metastrongylus spp. and Stephanurus dentatus. Efficacy was evaluated against the louse Haematopinus suis in six studies and against the mite Sarcoptes scabiei in four studies. A common study design was employed for each study type. In all studies, animals were allotted at random to a doramectin-treated or a saline-treated group. The doramectin-treated group received the drug at 300 micrograms kg-1 by intramuscular injection while the saline-treated group received saline by the same route. In the nematode studies, worm burdens were determined for each animal at slaughter 14-16 days after treatment. Efficacy against each nematode species/stage was assessed on the basis of percentage reduction in geometric mean worm burden in doramectin-treated animals compared with saline-treated controls. In louse and mite studies, counts were made immediately before treatment and then at weekly intervals for four weeks. Efficacy was based on a comparison of the level of infestation on the day of treatment with that on the last day of test. Data from individual studies were combined to derive a single estimate of efficacy against each of the parasite species represented in the study program. Efficacy of doramectin was 98% or greater against all nematode species except T. suis for which the efficacy was 87% and 79% against adult and fourth larval stage, respectively. Efficacy was 100% against both Haematopinus suis and Sarcoptes scabiei.

Field evaluation of doramectin for treatment of gastrointestinal nematode infections and louse infestations of cattle.

OBJECTIVE: To evaluate the safety and efficacy of doramectin given by injection at a dosage of 200 micrograms/kg of body weight for treatment of gastrointestinal nematodiasis or louse infestations of cattle. ANIMALS: 1,031 mixed-breed cattle were treated in the nematode study and 418 were treated in the louse study. PROCEDURE: Naturally parasitized cattle were given 200 micrograms of doramectin/kg or an equivalent volume of saline solution, SC. In nematode experiments, fecal samples were collected from each animal 1 week before treatment, at time of treatment, and at weekly intervals there after for 3 weeks. In louse experiments, louse counts were carried out for each animal on the day of treatment and 14 and 28 days later. All cattle were weighted at the time of treatment and at the end of the experiment. RESULTS: By 21 days after doramectin treatment, fecal egg counts had decreased to zero in 9 of 10 experiments and to 1 egg/g in the remaining experiment. Differences between treatment groups were significant (P < 0.0001) in all instances. Pretreatment coproculture identified Haemonchus, Ostertagia, Cooperia, Trichostrongylus, and Nematrodirus as the represented genera. Doramectin was 100% effective in eliminating infestation with Linogna thus vituli, Haematopinus eurysternus, and Solenopotes capillatus. Infestation with the chewing louse Damalinia bovis was reduced overall by 86%. For all species, post treatment louse counts were significantly (P < 0.02) less for doramectin-treated cattle than for controls. Adverse reactions to doramectin were not apparent in either study. CONCLUSION AND CLINICAL RELEVANCE: Injectable doramectin at a dosage of 200 micrograms/kg is safe and effective for treatment of gastrointestinal nematodiasis and louse infestations of cattle under field conditions.

Pharmacokinetics and bioequivalence of parenterally administered doramectin in cattle.

Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 micrograms/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration (Cmax), and areas under the concentration curve (AUC0-infinity) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC0-infinity of 457 +/- 66 ng.day/mL (+/- SD) and a mean Cmax of 27.8 +/- 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC0-infinity of 475 +/- 82 ng.day/mL and a mean Cmax of 33.1 +/- 9.0 ng/mL. Absorption constants (ka) determined by modelling were 0.542 +/- 0.336 day-1 after sc administration and 0.710 +/- 0.357 day-1 after i.m. administration. The 90% confidence limits on the difference between mean AUC0-infinity values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. Cmax was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In(Tmax +1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.

Anticoccidial efficacy of semduramicin. 1. Evaluation against field isolates by dose titration in battery tests.

Semduramicin (AVIAX), a novel polyether ionophore, was titrated in a series of five battery tests at 20, 25, and 30 ppm in feed to determine the optimum level for use. Twelve-day-old broiler chicks were medicated for 48 h prior to inoculation in each 9-day test. The inocula included monospecific field isolates of Eimeria tenella, Eimeria brunetti, Eimeria necatrix, and Eimeria maxima, and a mixture of these species with Eimeria acervulina and Eimeria mitis. The numbers of oocysts inoculated were selected after titration of each species and the mixture of species. All three concentrations of semduramicin significantly (P < .05) reduced coccidiosis mortality and lesion scores and achieved lower feed:gain ratios and greater weight gains than the infected, unmediated treatments. A concentration of 25 ppm semduramicin was determined to be optimal based on improved lesion control compared with 20 ppm and improved weight gain compared with 30 ppm.

Anticoccidial efficacy of semduramicin. 2. Evaluation against field isolates including comparisons with salinomycin, maduramicin, and monensin in battery tests.

The efficacy of semduramicin (AVIAX), a novel polyether ionophore, was profiled in a series of 57 battery tests conducted in the United States and the United Kingdom. The studies employed mixed and monospecific infections of Eimeria acervulina, Eimeria mivati/Eimeria mitis, Eimeria brunetti, Eimeria maxima, Eimeria necatrix, and Eimeria tenella derived from North American and European field isolates. Ten-day-old broiler cockerels in pens of 8 to 10 birds were continuously medicated in feed beginning 24 h before challenge in tests of 6 to 8 days' duration. At the use level of 25 ppm, semduramicin effectively controlled mortality, lesions, and weight gain depression that occurred in unmedicated, infected controls for all species. In comparison with 60 ppm salinomycin, semduramicin significantly (P < .05) improved weight gain against E. brunetti and E. tenella, lesion control against E. brunetti and E. maxima, and the control of coccidiosis mortality against E. tenella. Salinomycin was superior (P < .05) to all treatments in maintenance of weight gain and control of lesions for E. acervulina. Maduramicin at 5 ppm was inferior (P < .05) to semduramicin in control of E. acervulina and E. maxima lesions, but was superior (P < .05) to all treatments in maintenance of weight gain and control of lesions in E. tenella infections. The data indicate that semduramicin at 25 ppm is well tolerated in broilers and possesses broad spectrum anticoccidial activity.

Activity of doramectin against nematode endoparasites of cattle.

A series of 28 controlled anthelmintic studies, involving 634 cattle, was conducted throughout North America and Europe to evaluate the efficacy of doramectin against a broad range of gastrointestinal parasitic nematode species and lungworms in naturally and experimentally infected animals. Within each study, one or two groups were treated with doramectin at 200 micrograms kg-1 and another group received no drug treatment. Worm burdens were estimated by standardised techniques, and efficacy assessed on reduction of worm burdens in doramectin-treated animals. Doramectin was at least 99.6% effective (P < 0.0002) in eliminating the immature and adult stages of the following 14 species of nematodes: Ostertagia ostertagi (including inhibited), Ostertagia lyrata, Haemonchus placei, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia oncophora (including inhibited), Cooperia pectinata, Cooperia punctata, Cooperia spatulata, Cooperia surnabada, Bunostomum phlebotomum, Strongyloides papillosus, Oesophagostomum radiatum and Dictyocaulus viviparus. Efficacy against adult Trichostrongylus longispicularis, Nematodirus spathiger and Trichuris spp. was 93.1%, 96.5% and 94.6%, respectively. Efficacies against adult and fourth-stage larvae of Nematodirus helvetianus, the dose-limiting species, were 73.3% and 75.5%, respectively.

Spectrum of activity of doramectin against cattle mites and lice.

A series of 16 studies was conducted involving 288 cattle with naturally acquired or experimentally induced mite or louse infestations to evaluate the efficacy of doramectin. Four studies were conducted against the mite species Psoroptes bovis and two against the mite species Sarcoptes scabiei. Ten studies involved cattle with one or more of the following louse species: Damalinia bovis, Haematopinus eurysternus, Linognathus vituli and Solenopotes capillatus. In each study, a group of at least nine but not more than 25 cattle were randomly allocated to a control or a treated group. One group was treated with doramectin at 200 micrograms kg-1 and the other group received no medication. Mites or lice were quantified by species immediately before treatment and at weekly intervals for 4 weeks thereafter. Doramectin was 100% efficacious against infestations of P. bovis, Sarcoptes scabiei, H. eurysternus, L. vituli and Solenopotes capillatus. The drug reduced infestations of D. bovis by a mean of 82%.