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PubMed1989

[The effect of ivermectin on reactivated somatic larva of Ancylostoma caninum Ercolani 1859 (Ancylostomidae) in the pregnant dog].

It was evaluated by means of a controlled test to what extent reactivated larvae of Ancylostoma caninum were influenced by single or double treatment with ivermectin. The investigations were done with a total of ten experimentally infected bitches. The single treatment of dams two to ten days ante partum with 0.5 mg or 1 mg ivermectin per kg bodyweight reduced the wormburden of their puppies on an average by 96.6% and 98.5%, respectively. The double treatment with 0.5 mg/kg bodyweight ante and post partum each with an interval of ten days completely prevented lactogenic infections with Ancylostoma caninum. Following a single application of 0.5 mg ivermectin per kg bodyweight the excretion of larvae was markedly delayed and remained on a low level. In addition the infections of the puppies of single treated dams became patent on an average 9.5 and 14.5 days later than the controls. In the bitches no side-effects, neither local nor general, were seen after the treatment with ivermectin. All forty puppies of the treated bitches were born without visible damages.

Ancylostoma↗
PubMed1997

Successful use of ivermectin in the treatment of endemic scabies in a nursing home.

Ivermectin, an antiparasitic agent, was successfully used as a sole agent to combat endemic scabies in a closed 33-bed ward of a rural nursing home. Previous topical therapies, including multiple applications of permethrin, gamma-benzene hexachloride, benzyl benzoate and precipitated sulfur in white soft paraffin, had failed. Several patients exhibited hyperkeratotic crusted scabies with head and neck involvement and all residents except one recently arrived resident had evidence of active infestation. All residents were treated with 200 micrograms/kg of ivermectin and this dose was repeated 2 weeks later in all subjects. Four weeks after the first dose of ivermectin there was no evidence of active scabies and all rashes were totally resolved by 6 weeks. The action of ivermectin, its safety and its indications are discussed.

Administration, Oral↗
PubMed1989

Ivermectin treatment of onchocerciasis.

Ivermectin is a recently developed macrocyclic lactone that has widespread antiparasitic activity. A series of clinical trials has shown that ivermectin is safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction as is seen with diethylcarbamazine treatment. The drug also temporarily interrupts production of microfilaria but has no known long-lasting effects on the adult worms. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement. At this dose, ivermectin causes minimal side effects and appears to be sufficiently free of severe adverse reactions to be used on a mass scale. Its use promises to revolutionise the treatment of onchocerciasis.

Animals↗
PubMed1999

Cyclosporin A and trifluoperazine, two resistance-modulating agents, increase ivermectin neurotoxicity in mice.

The P-glycoprotein expressed in the blood-brain barrier has been associated with the restricted access of many compounds to the central nervous system. Mice lacking the mdr1a P-glycoprotein gene show an accumulation of various drugs in brain tissues. P-glycoprotein is also correlated with the phenomenon of multidrug resistance in tumour cells. To investigate the effects of drugs that modulate multidrug resistance in the selective permeability of the blood-brain barrier, mice were treated with cyclosporin A or trifluoperazine plus ivermectin, a P-glycoprotein substrate, that has a limited access to the central nervous system. When mice received an injection of cyclosporin A (50 mg/kg, intraperitoneally) or trifluoperazine (750 microg/kg, intraperitoneally) one hour prior to the administration of ivermectin (10-15 mg/kg, intraperitoneally) there was an increase in the acute toxicity of ivermectin. HPLC analysis of brain tissues indicated that the ivermectin brain concentration was 2.5 times higher when mice were previously treated with cyclosporin A (50 mg/kg). These results suggest that attention should be given to the side effects of drugs that interact with P-glycoprotein and are commonly used clinically and also to the possibility of creating a pharmacological gap in the blood-brain barrier that allows the access of chemotherapeutic drugs to brain tumours.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1986

Treatment of equine onchocerciasis with ivermectin paste.

A single oral dose of ivermectin paste was administered to 12 horses with dermatitis and clinical signs typical of onchocerciasis. Two of the horses also had lesions of Queensland itch. Microfilarias of Onchocerca cervicalis were identified in fresh, macerated, skin biopsies from the neck, brisket or umbilical regions of all horses and microfilarias of O. gutturosa from the neck of 2. Eight of the horses developed skin reactions 4 to 24 h after the administration of the ivermectin, notably weals over the neck, shoulders and flanks and pitting oedema of the ventral midline and intermandibular space. Regression of the onchocerciasis lesions was evident within 7 days of treatment and affected skin had returned to normal within 3 months. The lesions of Queensland itch were not affected by the ivermectin treatment. Microfilarias were present in biopsies of skin, particularly in the superficial dermis, before treatment, but were absent from all skin biopsies taken one week after treatment. In some horses transient skin sensitivity reactions developed. Microfilarias began to reappear in the biopsies of some of the horses 2 months after treatment. It is concluded that the oral paste formulation of ivermectin, although not effective against adult onchocerca, is useful for the therapeutic control of microfilarias in the skin lesions of equine onchocerciasis.

Animals↗
PubMed1994

Rainfall and breed effects on the efficacy of ivermectin jetting fluid for the prevention of fly strike and treatment of infestations of lice in long-wooled sheep.

An ivermectin-based jetting fluid was assessed for its efficacy in the prevention of blowfly strike and treatment of lice in long-wooled sheep. The ivermectin concentrate was diluted to 0.03 mg/mL and applied via a standard hand jetting technique. In insectary studies, using laboratory-reared Lucilia cuprina, sheep jetted with ivermectin were protected from induced breech and body strikes for 18 weeks after treatment. Merino and Corriedale sheep were equally protected, as were sheep subjected to 25 mm simulated rainfall at 1, 3 or 6 hours after jetting. Naturally occurring infestations of lice, Bovicola (Damalinia) ovis, were successfully treated with ivermectin jetting fluid in Merino and Corriedale sheep using a standard hand jetting technique. In addition, the efficacy of treatment was not affected by simulated rainfall at 1, 3 or 6 hours after treatment.

Administration, Topical↗
PubMed1996

Effects of drug residues in the faeces of cattle treated with injectable formulations of ivermectin and moxidectin on larvae of the bush fly, Musca vetustissima and the house fly, Musca domestica.

OBJECTIVE: To assess the toxicity of residues of ivermectin and moxidectin in cattle faeces collected at intervals after treatment. DESIGN: Replicated bioassays of faeces using larvae of the bush fly, Musca vetustissima and the house fly, Musca domestica. ANIMALS: Two groups of five Murray Grey x Aberdeen Angus steers were treated with injectable formulations of ivermectin and moxidectin respectively. A third group was used as an untreated control. PROCEDURE: Newly emerged fly larvae were reared in the dung of treated animals. RESULTS: Drug residues in faeces collected 3 to 35 days after treatment with an injectable formulation of moxidectin had no significant effect on the survival of larvae of M vetustissima. Similarly, faeces dropped up to seven days after treatment caused no significant reduction in larval survival in M domestica. In day 2 dung, residues of moxidectin delayed development of M vetustissima larvae, but had no effect on their survival. In contrast, ivermectin-treated steers, produced dung that inhibited larval development of both M vetustissima and M domestica for 7 to 14 days after treatment. Significant reductions in survival of M vetustissima larvae occurred in dung collected on days 21 and 28 after treatment, but by day 35 survival did not differ from that in control dung. CONCLUSION: Excreted faecal residues of moxidectin are relatively innocuous to larvae of both M vetustissima and M domestica. Those of ivermectin inhibit survival for 7 to 14 days after treatment and are likely to have adverse effects on non-target organisms.

Animals↗
PubMed2001

The development and survival of three species of coprophagous insect after feeding on the faeces of sheep treated with controlled-release formulations of ivermectin or albendazole.

OBJECTIVE: To assess the toxicity from residues of controlled-release formulations of ivermectin and albendazole to insects that feed on sheep faeces. ANIMALS: In two consecutive years, groups of sheep were treated with controlled-release capsules of ivermectin or albendazole. Untreated sheep were used as controls. PROCEDURES: Larvae of the bush fly, Musca vetustissima, and adults and larvae of the dung beetles, Onthophagus taurus and Euoniticellus fulvus were fed on faeces collected at intervals after drug treatment. In assays using beetles, treatment effects were assessed by comparing numbers of eggs laid, survival of juveniles and survival of mature and immature adults. Survival at time of pupariation was used in assays on flies. RESULTS AND CONCLUSIONS: Faeces from sheep treated with albendazole had no detectable effects on breeding by either flies or beetles. In contrast, faeces voided by sheep treated with controlled-release capsules of ivermectin (CRI) precluded successful breeding by each of the species tested. No fly larvae and almost no beetle larvae survived in faeces collected up to 39 days after capsule administration. Newly-emerged O taurus also suffered significant mortality whereas those that survived underwent delayed sexual maturation. Ivermectin residues had no effect on the survival of sexually mature beetles, but reduced the fecundity of O taurus. A model simulating the effects of drug residues on dung beetle populations indicates that CRIs have the potential to cause substantial declines in beetle numbers, particularly if treatment coincides with spring emergence.

Albendazole↗
PubMed1998

Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor.

We report that preapplication of ivermectin, in the micromolar range, strongly enhances the subsequent acetylcholine-evoked current of the neuronal chick or human alpha7 nicotinic acetylcholine receptors reconstituted in Xenopus laevis oocytes and K-28 cells. This potentiation does not result from nonspecific Cl- currents. The concomitant increase in apparent affinity and cooperativity of the dose-response curve suggest that ivermectin acts as a positive allosteric effector. This interpretation is supported by the observation of an increase in efficiency of a partial agonist associated with the potentiation and by the differential effect of ivermectin on mutants within the M2 channel domain. Ivermectin effects reveal a novel allosteric site for pharmacological agents on neuronal alpha7 nicotinic acetylcholine receptors.

Allosteric Regulation↗
PubMed1988

Effect of single-dose ivermectin therapy on human Onchocerca volvulus infection with onchocercal ocular involvement.

Ivermectin has shown promise as a potentially safe and effective microfilaricidal drug for the treatment of onchocerciasis. Several limited studies have shown it to have fewer side effects, especially ocular complications, than the currently available drug, diethylcarbamazine. The detailed ocular findings in 200 moderately to heavily infected Liberians who were enrolled in a safety and dose-finding study are presented. They received either 0, 100, 150, or 200 micrograms/kg of ivermectin and were followed up for 12 months. In clinical studies so far carried out ivermectin in a dose of 100, 150, or 200 micrograms/kg has not been associated with any major adverse reactions nor were there any sight-threatening effects even in the presence of severe ocular disease. Each of these doses significantly reduced the ocular microfilaria load for at least 12 months when compared with either the placebo (p less than 0.05) or pretreatment values (p less than 0.001). However, the 100 and 150 micrograms/kg doses caused fewer minor side effects than the higher dose. These results confirm that ivermectin in a single oral dose may be a safe and effective microfilaricidal drug for the treatment of onchocerciasis and that it appears to be free of major ocular side effects.

Adolescent↗
PubMed1997

Efficacy of moxidectin, ivermectin and albendazole oral drenches for suppression of periparturient rise in ewe worm egg output and reduction of anthelmintic treatment for lambs.

Sixty multiparous crossbred ewes which had lambed within three days in the first week of April 1996, were divided into four groups. Each group consisted of 15 ewes plus 12 pairs of twins and three single lambs. Group 1 was left untreated, group 2 was treated with albendazole 2.5 per cent drench, group 3 received moxidectin 0.1 per cent drench and group 4 received ivermectin 0.08 per cent drench. The ewes in each group were dosed with their anthelmintic on April 4 (day 0) before being turned out to separate equal-sized paddocks within the same field on the following morning. The field had been used for grazing sheep annually for many years and was considered to be contaminated with infective larvae of the common gastrointestinal nematodes infecting sheep in the region. Faecal samples were collected every two weeks from the ewes and lambs until July 25 (day 112). The lambs in each group were dosed with the anthelmintic used for their dams on day 42, and the dose was repeated when more than 50 per cent of the lambs in any group had a faecal egg count of more than 200 eggs per gram (epg). The total faecal egg output of the treated ewes over days 14 to 70, compared with that of the untreated control group, was reduced by 78.9 per cent by the moxidectin drench, by 47.6 per cent by ivermectin, and by 21.5 per cent by albendazole. The lambs in the groups treated with moxidectin and ivermectin required only one treatment on day 42 before reaching finishing weight; those in the albendazole-treated group were treated twice and the control group once. The faecal egg outputs of the lambs from day 42 until the end of the experiment on day 112 were reduced by 75 per cent by the moxidectin drench, by 48.5 per cent by ivermectin, and by 9 per cent by albendazole. There were no significant differences between the rates of weight change of either ewes or lambs in any of the groups.

Albendazole↗
PubMed1998

Persistence of the activity of topical ivermectin against biting lice (Bovicola bovis).

To assess the persistence of the activity of topical ivermectin against a natural challenge with biting lice (Bovicola bovis), 90 mixed-breed cattle that had been treated to remove lice, were blocked by bodyweight within sex and randomly allocated to three treatments: untreated control, doramectin at 200 micrograms/kg by subcutaneous injection, and ivermectin at 500 micrograms/kg by topical application. Forty-five pens were blocked into three groups of 15, and the blocks of pens were randomly allocated to three 14-day challenge periods starting 21, 28 and 35 days after treatment. There were five pens per treatment for each challenge period, and one B bovis-infested donor calf was introduced into each pen containing two principal calves at the start of the challenge period for that block of pens. The calves were examined thoroughly for B bovis seven, 14 and 21 days after the introduction of the donors. There were no significant differences between the control and doramectin groups for the numbers of animals infested, or the geometric mean louse counts at the final examination for any of the challenge periods. At the final examination for each challenge period, the louse counts of the cattle treated with topical ivermectin were all zero, and significantly (P < 0.05) fewer cattle treated with topical ivermectin were infested than either the controls or cattle treated with doramectin.

Animals↗
PubMed2002

Pharmacokinetics of ivermectin in llamas (Lama glama).

The pharmacokinetic behaviour of ivermectin was investigated in adult llamas (Lama glama) by using high performance liquid chromatography with a lower limit of quantification of 2 ng/ml to measure its concentration in serum. Llamas were treated with one of three commercial formulations (injectable, pour-on or oral paste) at dosages recommended by the manufacturer, or with an experimental injectable sustained-release formulation. In five llamas given 1 per cent ivermectin subcutaneously at 200 microg/kg, the median peak serum concentration (Cmax) was 3 ng/ml and the area under the serum concentration-time curve (AUC) was 13.5 ng x day/ml. In six llamas treated topically with 0.5 per cent ivermedin pour-on at 500 microg/kg, Cmax was 2.5 ng/ml or less and the AUC was 7.75 ng x day/ml or less. In seven llamas with measurable concentrations of ivermedin, the median times to peak serum concentration (tmax) were six days after subcutaneous injection and seven days after treatment with the pour-on formulation. In six llamas, the serum concentration of ivermectin remained less than 2 ng/ml for 124 hours after treatment with a 1.87 per cent oral paste at 200 microg/kg. In five llamas treated subcutaneously with 25 per cent ivermectin sustained-release microspheres at 1500 microg/kg, the median Cmax was 5 ng/ml and the median AUC was 224 ng x day/ml.

Animals↗
PubMed2001

Development of reactive onchocercal skin lesions during a placebo-controlled trial with ivermectin among persons without lesions at baseline.

Clinical trials of the effects of ivermectin on onchocercal skin disease have documented reduction in itching, but a less than clear benefit on reactive skin lesions. It has been suggested that one of the positive effects might be the prevention of new lesions. A study among a rural adult farming population in southwestern Nigeria provided ivermectin in three treatment groups and a placebo to community members who were examined and treated at 3-monthly intervals over a 15-month period. Among the 1206 people recruited for the study, 627 (52%) had no lesions at baseline examination. Atotal of 291 participants without baseline lesions attended all five follow-up examinations, and only their results were analysed. Members of all four groups developed new lesions, but those receiving ivermectin had a consistently lower proportion of lesions than the placebo group. This difference reached statistical significance at the 5% level in three of the five periods and was below the 10% level at the other two periods. These findings are suggestive of an inhibiting effect of ivermectin among those without lesions at the beginning of a community treatment programme, and justify community treatment as a way of limiting morbidity and social stigma associated with these lesions.

Adult↗
PubMed1984

Effect of ivermectin treatment on eosinophilic pneumonia and other extravascular lesions of late Strongylus vulgaris larval migration in foals.

Eighteen parasite-free pony foals were infected orally with 500 third stage larvae of Strongylus vulgaris. At 56 days after infection, six ponies were treated with intramuscular ivermectin (22, 23-dihydroavermectin B1); six were treated with oral ivermectin; and six were not treated. Necropsy was done 91 days after infection to study the pathologic effects of migrating S. vulgaris larvae and to determine the efficacy of ivermectin in attenuation of S. vulgaris-induced lesions. Larval migration induced eosinophilic inflammation of the liver, spleen, mesenteric, colic and cecal lymph nodes, and small and large intestine. Previously unreported parasitic lesions included eosinophilic pneumonia with eosinophilic granulomas and pulmonary lymphoid nodules. S. vulgaris larvae were observed in eosinophilic granulomas in the lung, epicardium, liver, and intestinal serosa. Injectable and oral ivermectin formulations were equally effective in reduction of these lesions.

Animals↗
PubMed2003

Ivermectin for the treatment of resistant scabies.

OBJECTIVE: To assess the clinical literature describing the use of ivermectin in cases of treatment-resistant scabies infestations. DATA SOURCES: Clinical literature accessed through a MEDLINE search (1966-July 2001) and the Cochrane Database. DATA SYNTHESIS: A limited number of case reports and case series describes successful intervention with ivermectin use in patients who have failed prior therapy. Ivermectin may serve as a viable alternative therapy as the incidence of resistant scabitic infestations increases. CONCLUSIONS: Ivermectin appears to be a safe and effective alternative for patients with treatment-resistant scabies. Larger, controlled clinical trials are required before this therapy can be recommended in the general population or as primary therapy.

Aged↗
PubMed1990

Ivermectin: a long-acting microfilaricidal agent.

Ivermectin is a macrocyclic lactone (fermentation) product and actinomycete (Streptomyces avermitilis) that possesses an unusually broad spectrum of potent activity against several species of nematodes, arachnids, and insects that parasitize domestic animals. From clinical trials in humans it has been found to be microfilaricidal, killing microfilariae of Onchocerca volvulus (the parasite causing onchocerciasis), and interrupting its transmission by the black fly vector. Dermal microfilariae density in patients are reduced to near zero levels for 6-12 months after a single oral dose of ivermectin 0.15-0.2 mg/kg. Its precise mechanism of action is unknown. It has a time to maximum concentration of 2.7-4.3 h, and an elimination half-life of 28 +/- 10 h. When compared with an oral solution the tablet dosage form has a relative bioavailability of approximately 60 percent. Not much is known about its metabolism in humans, and the unchanged drug is not detected in the urine. Controlled clinical trials have shown ivermectin to be associated with milder side effects than diethylcarbamazine, the current drug of choice for onchocerciasis therapy. It does not cause the severe Mazzoti-type (anaphylactoid) reactions that are associated with diethylcarbamazine use. Ivermectin is effective, safer, and more tolerable than diethylcarbamazine. It should, therefore, replace diethylcarbamazine as the drug of choice for onchocerciasis therapy.

Animals↗
PubMedDate not supplied

Review of ivermectin in scabies.

BACKGROUND: Currently available topical medications for scabies are messy and need prolonged application. This leads to poor patient adherence. Emerging drug resistance to topical scabicides has made eradication of scabies difficult. OBJECTIVE: Availability of an effective oral scabicidal agent, ivermectin (Ivm), opens a new era in the management of scabies. This review summarizes the published literature on the use of ivermectin in the treatment of scabies. CONCLUSION: A single oral dose of ivermectin of 200 mg/kg body weight is very effective in the treatment of human scabies. A second dose 7-10 days later substantially improves the cure rate. This suggests that ivermectin may not be effective against all the stages in the life cycle of the parasite. Endemic and epidemic scabies in institutions are better treated with Ivm. Crusted scabies ideally should be treated with a combination of Ivm and topical scabicides. Other standard measures and precautions should be taken. Additional controlled studies using a higher single oral dose or using parenteral or topical forms of Ivm are needed. The safety of Ivm in children less than 5 years old and in pregnant women has to be established. The U.S. FDA has not yet approved the drug for the treatment of human scabies.

Humans↗