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PubMed1989

Ivermectin plasma concentrations in collies sensitive to ivermectin-induced toxicosis.

Five Collies sensitive to toxic effects of ivermectin and 7 nonsensitive Collies were given 100 micrograms of ivermectin/kg of body weight, PO. Blood samples were collected from each dog before treatment; at posttreatment hours 1, 2, 3.5, 5, and 8; and at posttreatment days 1, 2, 4, 7, 14, and 21. Each sample was assayed for ivermectin concentration, and statistical analyses were performed on the resulting plasma concentration data to determine differences in absorption and clearance of drugs between the 2 groups. Variables measured were area under the curve (using the trapezoidal rule), peak plasma concentration, and the time to peak concentration. Differences between sensitive and nonsensitive Collies for variables analyzed were not significant (P greater than 0.05).

Absorption↗
PubMed1984

Ivermectin and an ivermectin-penicillin combination: a comparison of anthelmintic efficacy in horses.

Ivermectin given IM at 200 micrograms/kg, alone or in combination with procaine penicillin G at 600 IU/kg, to 20 randomly selected young horses of various breeds reduced fecal strongyle egg counts from 400-4100 epg (avg greater than 1000) pretreatment to zero 7 days posttreatment. There were no systemic or injection-site reactions, either immediate or delayed, in any of the horses.

Animals↗
PubMed1991

Solubilization and characterization of a high affinity ivermectin binding site from Caenorhabditis elegans.

Ivermectin is a member of the avermectin family of compounds that are used to treat helminth and arthropod diseases in humans, domestic animals, and plants. A membrane-bound high affinity ivermectin binding site was extracted from Caenorhabditis elegans with the nonionic detergent 1-O-n-octyl-beta-D-glucopyranoside. The free-living nematode C. elegans is highly sensitive to the avermectins and was used as a model of parasitic nematodes. The membrane-bound and detergent-solubilized ivermectin binding sites are stable and exhibit high affinity binding, with dissociation constants of 0.11 nM and 0.20 nM, respectively. The maximum binding of [3H]ivermectin is 0.54 pmol/mg of membrane protein and 0.66 pmol/mg of detergent-soluble protein. Kinetic analysis of ivermectin binding shows that the ivermectin binding sites form a slowly reversible complex with ivermectin. The rates of dissociation of [3H]ivermectin with the solubilized and membrane-bound binding sites are 0.005 min-1 and 0.006 min-1, respectively. The association rate of the soluble binding site is 0.053 nM-1 min-1, slightly slower than that observed for the membrane-bound site, 0.074 nM-1 min-1. To characterize the ivermectin binding site, competition experiments were performed by inhibiting [3H]ivermectin binding with several avermectin derivatives and the neurotransmitter gamma-aminobutyric acid (GABA). The order of potency was 22,23-dihydroavermectin B1a monosaccharide greater than 22,23-dihydroavermectin B1a aglycone greater than 3,4,8,9,10,11,22,23-octahydro B1 avermectin for both the membrane-bound and NOG-soluble binding sites. GABA did not compete with ivermectin binding, although it has been suggested that ivermectin acts at the GABA-gated chloride channel in some invertebrate systems. Optimum ivermectin binding and assay conditions have been determined. The detergent-soluble ivermectin binding site appears to be negatively charged and has a pl of 4.0 and an apparent Mr in Triton X-100 micelles of 340,000. Detergent solubilization of a high affinity ivermectin binding site will enable the subsequent purification and characterization of a putative site of ivermectin action.

Animals↗
PubMed2003

Effect of repeated community-based ivermectin treatment on the intensity of onchocerciasis in Nigeria.

INTRODUCTION: Ivermectin (Mectizan) is an effective and well-tolerated microfilaricidal drug that has emerged as the drug of choice for large-scale treatment of onchocerciasis. Repeated doses of ivermectin is reported to lower the incidence of microfilardermia, while a single dose will markedly reduce skin microfilarial loads for up to 12 months with a transient fall in microfilarial level. AIM: The aim of the study was to evaluate the effect of repeated community-based ivermectin treatment on the intensity of onchocerciasis in 10 onchocerciasis-endemic communities of Lade District, Pategi Local Government Area of Kware State, Nigeria. METHODS: The participants, a cohort of 330 men from whom parasitologic pre-treatment data were collected before mass ivermectin distribution commenced in 1992, were evaluated just before the fifth round of annual ivermectin treatment in August-September 1996, and 12 months after the fifth round in August-September 1997. Two bloodless skin snips were obtained from participants' left and right iliac crests and incubated for 24 h in an 0.5 mL microfuge tube containing 0.2 mL normal saline, before microscopic examination and enumeration of microfilariae. The community microfilarial load (CMFL), the most sensitive parasitologic indicator, was computed. RESULTS: Following four rounds of repeated annual treatments of onchocerciasis with ivermectin in the 10 communities studied, varying degrees of reduction in CMFL were observed in six of the 10 communities. These reductions were significant in three of the six communities at the first evaluation carried out just before the fifth round of annual ivermectin treatment (p = or <0.05). There was an increase in the remaining four communities, mainly attributed to poor annual acceptance and compliance with annual ivermectin treatment due to the occurrence of severe adverse reactions and absenteeism. Post-treatment evaluation (12 months after the previous evaluation), just before the sixth round of annual ivermectin treatment was preceded by community mobilization (enlightenment on the usefulness of ivermectin an assurance on its safety), especially in the four affected communities. This brought about reductions in the CMFL in the four communities that were not previously affected. Although the CMFL of these four communities was reduced, the CMFL of three of the communities did not fall below the 1992 pre-treatment level but was below the level recorded 12 months earlier. One of these affected communities had its CMFL reduced below the 1992 pre-treatment CMFL. CONCLUSION: This study confirms the efficacy of ivermectin in the reduction of CMFL but exposes the danger of failing to monitor annual ivermectin treatment where community ivermectin-based control efforts are ongoing. The results obtained from this study are not as impressive as results reported from closely monitored scientific evaluations of ivermectin efficacy studies.

Journal Article↗
PubMed2005

Predictors of compliance with community-directed ivermectin treatment in Uganda: quantitative results.

In order to identify the factors influencing compliance with mass ivermectin treatment for onchocerciasis control, a cross-sectional study was carried out in Bushenyi District, Uganda. Data were collected by interviewing 839 individuals who were randomly selected from 30 clusters where onchocerciasis is endemic. Information was collected on compliance with ivermectin treatment, socio-demographic characteristics, perception of personal susceptibility to onchocerciasis, knowledge about cause/transmission of onchocerciasis, knowledge of signs and symptoms of onchocerciasis, treatment of onchocerciasis, benefits and dangers of taking ivermectin, organization of distribution of ivermectin, work and selections of community drug distributors (CDDs), social influence and support to take ivermectin and on barriers and supports towards compliance with ivermectin treatment. The major factors favouring compliance were: perceiving CDDs as doing their work well, believing that measuring height is the best way to determine one's dose of ivermectin, having social support from one's family, saying that ivermectin treatment costs nothing, perceiving personal risk of onchocerciasis, believing that ivermectin prevents onchocerciasis and perceiving radios as supporting treatment with ivermectin. The strongest predictor of compliance with ivermectin treatment is perceiving CDDs as doing their work well with adjusted odds ratios of 5.54 (95% CI: 3.19-9.62). In order to improve compliance with ivermectin treatment, CDDs need to be well-facilitated and ivermectin distribution should be free. Health education is necessary so that people perceive themselves to be at risk of onchocerciasis and to understand the rationale of using height for dose determination. The health education should target the family and use radios.

Adult↗
PubMed1999

Effects of ivermectin and midecamycin on ryanodine receptors and the Ca2+-ATPase in sarcoplasmic reticulum of rabbit and rat skeletal muscle.

1. Ryanodine receptor (RyR) Ca2+ channels in the sarcoplasmic reticulum (SR) of skeletal muscle are regulated by the 12 kDa FK506- (or rapamycin-) binding protein (FKBP12). Rapamycin can also activate RyR channels with FKBP12 removed, suggesting that compounds with macrocyclic lactone ring structures can directly activate RyRs. Here we tested this hypothesis using two other macrocyclic lactone compounds, ivermectin and midecamycin. 2. Rabbit skeletal RyRs were examined in lipid bilayers. Ivermectin (cis, 0.66-40 microM) activated six of eight native, four of four control-incubated and eleven of eleven FKBP12-'stripped' RyR channels. Midecamycin (cis, 10-30 microM) activated three of four single native channels, six of eight control-incubated channels and six of seven FKBP12-stripped channels. Activity declined when either drug was washed out. 3. Neither ivermectin nor midecamycin removed FKBP12 from RyRs. Western blots of terminal cisternae (TC), incubated for 15 min at 37 C with 40 microM ivermectin or midecamycin, showed normal amounts of FKBP12. In contrast, no FKBP12 was detected after incubation with 40 microM rapamycin. 4. Ivermectin reduced Ca2+ uptake by the SR Ca2+-Mg2+-ATPase. Ca2+ uptake by TC fell to approximately 40% in the presence of ivermectin (10 microM), both with and without 10 microM Ruthenium Red. Ca2+ uptake by longitudinal SR also fell to approximately 40% with 10 microM ivermectin. Midecamycin (10 microM) reduced Ca2+ uptake by TC vesicles to approximately 76% without Ruthenium Red and to approximately 90 % with Ruthenium Red. 5. The rate of rise of extravesicular [Ca2+] increased approximately 2-fold when 10 microM ivermectin was added to TC vesicles that had been partially loaded with Ca2+ and then Ca2+ uptake blocked by 200 nM thapsigargin. Ivermectin also potentiated caffeine-induced Ca2+ release to approximately 140% of control. These increases in Ca2+ release were not seen with midecamycin. 6. Ivermectin, but not midecamycin, reversibly reduced Ca2+ loading in four of six skinned rat extensor digitorum longus (EDL) fibres to approximately 90%, and reversibly increased submaximal caffeine-induced contraction in five of eight fibres by approximately 110% of control. Neither ivermectin nor midecamycin altered twitch or tetanic tension in intact EDL muscle fibres within 20 min of drug addition. 7. The results confirm the hypothesis that compounds with a macrocyclic lactone ring structure can directly activate RyRs. Unexpectedly, ivermectin also reduced Ca2+ uptake into the SR. These effects of ivermectin on SR Ca2+ handling may explain some effects of the macrolide drugs on mammals.

Animals↗
PubMed1993

Dung dispersal and grazing area following treatment of horses with a single dose of ivermectin.

Environmental consequences of treating horses with recommended dosages of ivermectin paste were studied in two controlled experiments with 29 horses in Ohio. In 1988, dung dispersal rates were measured by changes in dry weight over time of 48 copromes (300 g) formed from feces taken from four treatment and four control horses 3 days post ivermectin treatment. There was delayed dispersal of copromes from horses treated with ivermectin in June, resulting in significantly heavier ivermectin copromes compared with those of control horses by September. There was no difference in ivermectin or control copromes after treatment in August. In 1989, the effects of treating horses with oral ivermectin or oxibendazole compared with untreated controls were quantified in a study with 21 horses under natural grazing conditions after treatment on 7 June. Sequential measurements of dung pat circumferences from 20 June 1989 to 7 March 1990 showed highly significant differences between ivermectin and control pats and between ivermectin and oxibendazole pats. Reductions in mean dung pat diameters did not occur in ivermectin pats until 11 October, when there was a 4.1% reduction compared with 35.1% for control pats and 37.2% for oxibendazole pats. By the end of the study, there was a 24.7% reduction in ivermectin pats compared with 59.1% and 59.9% for control and oxibendazole pats respectively. In addition, there were significantly more pats showing complete dispersal in oxibendazole or control plots than in ivermectin plots. The calculated grazing area lost to feces was three times greater for ivermectin plots than for oxibendazole or control plots. It is suggested that environmental effects of the avermectins can be reduced by more rational use of anthelmintics.

Animals↗
PubMed2005

Interaction of ivermectin with multidrug resistance proteins (MRP1, 2 and 3).

Ivermectin is a potent antiparasitic drug from macrocyclic lactone (ML) family, which interacts with the ABC multidrug transporter P-glycoprotein (Pgp). We studied the interactions of ivermectin with the multidrug resistance proteins (MRPs) by combining cellular and subcellular approaches. The inhibition by ivermectin of substrate transport was measured in A549 cells (calcein or 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, BCECF) and in HL60-MRP1 (calcein). Ivermectin induced calcein and BCECF retention in A549 cells (IC(50) at 1 and 2.5microM, respectively) and inhibited calcein efflux in HL60-MRP1 (IC(50)=3.8microM). The action of ivermectin on the transporters ATPase activity was followed on membranes from Sf9 cells overexpressing human Pgp, MRP1, 2 or 3. Ivermectin inhibited the Pgp, MRP1, 2 and 3 ATPase activities after stimulation by their respective activators. Ivermectin showed a rather good affinity for MRPs, mainly MRP1, in the micromolar range, although it was lower than that for Pgp. The transport of BODIPY-ivermectin was followed in cells overexpressing selectively Pgp or MRP1. In both cell lines, inhibition of the transporter activity induced intracellular retention of BODIPY-ivermectin. Our data revealed the specific interaction of ivermectin with MRP proteins, and its transport by MRP1. Although Pgp has been considered until now as the sole active transporter for this drug, the MRPs should be taken into account for the transport of ivermectin across cell membrane, modulating its disposition in addition to Pgp. This could be of importance for optimizing clinical efficacy of ML-based antiparasitic treatments. This offers fair perspectives for the use of ivermectin or non-toxic derivatives as multidrug resistance-reversing agents.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1997

Randomised placebo-controlled comparison of ivermectin and albendazole alone and in combination for Wuchereria bancrofti microfilaraemia in Haitian children.

BACKGROUND: Lymphatic filariasis and intestinal helminth infections are important disorders in tropical areas. Periodic treatment with albendazole is now used in many school-based intestinal helminth-control programmes. However, few such programmes exist for lymphatic filariasis, despite evidence that single-dose treatment with ivermectin can greatly reduce the concentration of Wuchereria bancrofti microfilariae in the blood for months to years. We aimed to assess the potential for school-based control of lymphatic filariasis by investigating the efficacy and tolerability or combined ivermectin and albendazole in Haitian schoolchildren. METHODS: In January, 1996, we collected 832 20 microL capillary blood samples for inclusion in a randomised controlled study from children aged 5-11 years, and examined them by microscopy for W bancrofti microfilariae. Infected children were randomly assigned treatment with placebo (n = 29), a single 200-400 micrograms/kg dose of ivermectin (mean, 273 micrograms/kg, n = 28), 400 mg albendazole (n = 29), or a combination of 200-400 micrograms/kg ivermectin and 400 mg albendazole (n = 24). Children with high concentrations of microfilariae in the blood were admitted to hospital and adverse reactions were monitored for 3-5 days, otherwise children were examined at school or during a visit to their home. 4 months after treatment, we examined blood samples again for microfilariae. FINDINGS: 113 microfilaraemic children were enrolled (mean age 7.8 years). 4 months after treatment, the proportion of children who remained positive for microfilariae was significantly lower in the ivermectin plus albendazole group (four [17%]), but there were no significant changes in the other three groups (20 [69%] placebo, 22 [76%] albendazole alone, 17 [61%] ivermectin alone remained positive; p = 0.004). Geometric mean microfilarial concentration decreased from 9.3 to 5.3 per 20 microL blood among children who received placebo; from 15.5 to 1.5 per 20 microL blood among those who received ivermectin only (p = 0.032); from 14.1 to 5.1 per 20 microL blood among those who received albendazole alone; and from 13.7 to 0.3 per 20 microL blood among those who received both ivermectin and albendazole (p = 0.0001). Systemic adverse reactions did not differ significantly between children who received ivermectin alone and those who were treated with ivermectin and albendazole [corrected]. INTERPRETATION: For children with W bancrofti microfilaraemia, combined treatment with ivermectin and albendazole was more effective than treatment with ivermectin only, with no measurable increase in severity of adverse reactions.

Albendazole↗
PubMed2003

Amphidial structure of ivermectin-resistant and susceptible laboratory and field strains of Haemonchus contortus.

The development of anthelmintic resistance by nematode parasites is a growing problem for veterinarians, pet owners, 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. As a result, resistance to ivermectin, moxidectin, nemadectin, and doramectin by Haemonchus contortus has been documented throughout the world. Sensory neurons located in the cephalic end of nematodes are in close contact with the external environment. 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 strains of H. contortus with related selected, ivermectin-resistant strains and with a wild-type ivermectin-susceptible field strain of H. contortus from Louisiana reveal 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. These findings raise a number of questions regarding the relationship between amphidial structure and ivermectin resistance as well as the role of amphids as a means of entry for ivermectin. While shortened amphidial sensilla are associated with ivermectin resistance, it remains unclear if such a structural modification facilitates survival of nematodes exposed to macrocyclic lactones.

Animals↗
PubMed2002

Possible anxiolytic effects of ivermectin in rats.

Ivermectin, a mixture of 22,23-dihydroavermectin B1a (> or = 80%) and B1b (< or =20%), is produced by Streptomyces avermectilis, an actinomycete. It is a macrocyclic lactone disaccharide, a member of the avermectin family, and is used as an antiparasitic drug. Previous studies performed in our laboratory showed that doramectin, another avermectin drug, interferes with GABAergic-related behaviours, leading to anxiety and seizures. The objective of the present study was to examine the effects of ivermectin (0.5 and 1.0 mg/kg) on the central nervous system of rats, using behavioural models related to GABAergic neurotransmission. A known anxiolytic drug, diazepam, was used as a positive control. Open field and elevated plus-maze behaviours, as well as conflict behaviour to a conditioned response, were assessed. The effects of ivermectin and diazepam in reversing the anxiety induced by picrotoxin was studied. The protective effects of ivermectin on pentylenetetrazole- and picrotoxin-induced seizures were also investigated. In the open field, 1.0 mg/kg ivermectin decreased locomotion frequency at 15 and 60 min of observation, rearing behaviour showed a biphasic effect at 15 and 30 min and duration of immobility was increased in all sessions after 1.0 mg/kg ivermectin. These data suggest anxiolytic or sedative effects. Ivermectin and diazepam both had a tendency to cause an increase both in the number of entries into the open arms and on the time spent in the open arms of an elevated plus-maze. Picrotoxin on its own reduced the number of entries as well as the time spent in the open arms. Both diazepam and ivermectin reversed these effects of picrotoxin. In conflict behaviour analysis, ivermectin and diazepam gave the classic effect of an anxiolytic drug, reversing the conditioned response to shock. Ivermectin protected rats from the convulsant effects of pentylenetetrazole but not from those of picrotoxin. Thus, ivermectin had the pharmacological profile of an anxiolytic drug with GABAergic properties. The lack of effect on seizures induced by picrotoxin suggests that the action of ivermectin is different from that of the benzodiazepine drugs.

Animals↗
PubMed2001

Ivermectin excretion by isolated functionally intact brain endothelial capillaries.

1. Functionally intact brain endothelial capillaries were isolated from porcine brain. p-Glycoprotein was localized at the lumenal membrane of intact capillaries by immunohistochemistry using a murine monoclonal antibody and a secondary FITC fluorescent labelled anti-mouse IgG. Western blot staining of p-glycoprotein in isolated endothelial cells confirmed the immunohistochemistry. 2. Excretion of the fluorescent labelled anthelmintic drug Ivermectin (BODIPY-Ivermectin) was studied in the isolated brain endothelial capillaries. Drug accumulation in the capillary lumen was visualized by fluorescence confocal laser scanning microscopy and was measured by image analysis. Secretion of BODIPY-Ivermectin into the capillary lumen exhibited characteristics of specific and energy-dependent transport. Steady state lumenal fluorescence intensity averaged 1.6 times cellular fluorescence and was reduced 3--4 times below cellular levels when metabolism was inhibited by NaCN. 3. BODIPY-Ivermectin secretion was inhibited in a concentration-dependent manner by unlabeled Ivermectin. In addition, lumenal but not cellular fluorescence intensity was significantly decreased when capillaries were incubated with PSC-833, Cyclosporin A or Verapamil, all inhibitors of p-glycoprotein. Conversely, unlabelled Ivermectin reduced the p-glycoprotein (Pgp)-mediated secretion of a fluorescent derivative of Verapamil, (BODIPY-Verapamil). 4. BODIPY-Ivermectin secretion was not affected in the presence of Leucotriene C(4) (LTC(4)), a potent inhibitor of multidrug resistance related protein (mrp)-mediated transport processes. In addition, excretion of Fluorescein-Methotrexate, an mrp-substrate, was not inhibited by Ivermectin. 5. Uptake experiments with isolated porcine brain capillary cells showing increased cellular uptake of BODIPY-Ivermectin in the presence of unlabelled drug or PSC-833 supported the findings of a Pgp interaction in intact capillaries. 6. The data are consistent with BODIPY-Ivermectin and Ivermectin being transported across the lumenal membrane of brain capillaries. For the first time Pgp-interaction of Ivermectin at the blood brain barrier is demonstrated on a cellular level in an intact vascular tissue.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

A comparative study of the efficacy and tolerability of single and split doses of ivermectin and diethylcarbamazine in periodic brugian filariasis.

The use of ivermectin in lymphatic filariasis (both bancroftian and brugian) has been recently explored in several studies. We report in this paper, for the first time, a direct comparison of the efficacy and tolerability of single doses of ivermectin and diethylcarbamazine (DEC) in brugian filariasis. We also present our findings on the use of split doses of ivermectin and DEC on microfilaraemia levels and the occurrence of adverse reactions. Fifty male, asymptomatic microfilaremics drawn from the Alleppey District, Kerala, India, were allocated one of the following five treatment regimens in a double blind randomized study: (1) single oral 6 mg/kg dose of DEC; (2) single oral 6 mg/kg dose of DEC preceded by 1 mg/kg DEC primer; (3) single oral 220 micrograms/kg dose of ivermectin; (4) single oral 200 micrograms/kg dose of ivermectin preceded by a 20 micrograms/kg ivermectin primer; or (5) a single oral 400 micrograms/kg dose of ivermectin preceded by a 20 micrograms/kg ivermectin primer. The kinetics of microfilaria clearance differed in the two (DEC/ivermectin) groups in the first month post-treatment. At the end of 1 year there were no differences in the microfilaria levels in the two DEC-tested groups and the 420 micrograms/kg ivermectin group. The safety of the 400 micrograms/kg dose of ivermectin was established in this study which has also shown that, currently, this dose would be the best choice for brugian filariasis. Patients in the ivermectin groups had significantly lower adverse reaction scores than patients who had received DEC. There was no advantage in splitting the dose of either DEC or ivermectin, either in terms of efficacy or tolerability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1997

The effectiveness of a single treatment with doramectin or ivermectin in the control of gastrointestinal nematodes in grazing yearling stocker cattle.

Four studies were conducted to a similar experimental design in the U.S. to evaluate the effectiveness of doramectin injectable administered to yearling stocker cattle in the control of gastrointestinal nematodiasis over the subsequent grazing period. Studies were conducted in Wisconsin (WI) and Arkansas (AR) during the summer season. The other two studies were conducted in Georgia (GA) and Mississippi (MS) during the winter/spring season. Doramectin was compared with both ivermectin injectable and ivermectin pour-on in the WI study, with ivermectin injectable alone in the GA study and with ivermectin pour-on alone in the other two studies. At each study site, an area of permanent pasture previously grazed by parasitized animals was subdivided by fencing into equal pasture units each with its own water supply. A treatment designation (non-medicated control, doramectin injectable, ivermectin injectable or ivermectin pour-on) was randomly assigned to each pasture unit. Weaned beef calves with confirmed gastrointestinal nematode infections were randomly allotted to a pasture unit and corresponding treatment group. Each treatment group consisted of three replicates of seven animals per pasture unit (total 21 animals) in the WI study, three replicates of four or six animals per pasture unit (total 16 animals) in the AR study, five replicates of six animals per pasture unit (total 30 animals) in the GA study and three replicates of 12 animals per pasture unit (total 36 animals) in the MS study. Treatments were 1% doramectin injectable solution, 1% ivermectin injectable solution, 0.5% ivermectin pour-on solution or non-medicated controls. The injectables were administered at a dose of 1 ml/50 kg body weight (200 micrograms doramectin or ivermectin/kg) by subcutaneous injection in the neck. Ivermectin pour-on solution was administered topically at a dose of 1 ml/10 kg body weight (500 micrograms ivermectin/kg). After receiving their prescribed treatment, animals were placed on their designated pasture unit where they remained for the entire grazing period (84-140 days). Fecal nematode egg counts and body weights were monitored at predetermined intervals throughout each study. Doramectin treatment reduced pretreatment egg counts by between 95 and 100% by 21 days post-treatment. Subsequent rises in egg output from exposure to infective pastures were delayed by two to four weeks resulting in substantial reductions in total egg deposition over the grazing period and, therefore, potential pasture recontamination. Doramectin treatment resulted in substantial average daily weight gain advantages (0.152-0.272 kg) over the grazing season compared to non-medicated controls. Advantages were statistically significant (P < 0.05) in three of the four studies. There were no significant differences (P > 0.05) in average daily gain between the doramectin and ivermectin injectable or ivermectin pour-on treated groups.

Animal Feed↗
PubMed2002

Ivermectin: new indication. Oral treatment of scabies: simple and effective.

(1) Ivermectin is the first oral drug to be licensed in France for the treatment of scabies. (2) In common scabies, three small trials suggest that ivermectin is about as effective as topical preparations. (3) Several cohort studies have shown that ivermectin can control outbreaks of scabies (especially in institutions) and also in endemic areas. (4) There are no clinical trial data on ivermectin in crusted scabies. Case series suggest that combining ivermectin with topical treatments may increase efficacy. (5) Ivermectin seems to have few, mostly mild short-term side effects in adults. There are no reports of ivermectin treatment in infants weighing less than 15 kg or in breast-feeding infants. Data on about 400 pregnant women treated with ivermectin are reassuring. (6) In a small cohort of elderly patients, ivermectin used after topical preparations coincided with excess mortality 6 months later. Subsequent studies were reassuring, but all adverse events (including death) in elderly patients treated with ivermectin must none the less be notified. (7) In practice, oral ivermectin is effective against scabies and is thus an alternative to topical treatments. Its single-dose administration facilitates treatment, especially during outbreaks.

Administration, Oral↗