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PubMed1999

Epithelial transport of anthelmintic ivermectin in a novel model of isolated proximal kidney tubules.

PURPOSE: The mechanism of excretion of the anthelmintic drug ivermectin was investigated in a novel experimental model of functionally intact proximal tubules isolated from a teleost fish (Fundulus heteroclitus). METHODS: Secretion into the lumens of freshly isolated proximal tubules was studied by means of confocal laser scanning microscopy and digital image analysis using ivermectin and fluorescent labelled ivermectin (BODIPY-ivermectin; BI) as substrates. RESULTS: The tubular cells rapidly accumulated BI from the medium and attained steady state within 25 minutes. Luminal fluorescence in the steady state was 5-7 times higher as compared to intracellular fluorescence. The secretion of BI into the tubular lumens was inhibited in a dose dependent manner by unlabelled ivermectin and inhibitors of the renal excretory membrane pump p-glycoprotein, namely SDZ PSC-833 and verapamil, but not by leukotriene C4, a substrate of the renal export protein mrp2. Accumulation inside the tubular cells was not affected by the added inhibitors. Ivermectin inhibited the renal secretion of the fluorescent cyclosporin derivative NBDL-CS, a substrate of p-glycoprotein, but not the secretion of the mrp2-substrate fluorescein-methotrexate, nor the secretion of fluorescein, a substrate of the classical renal organic anion transporter. CONCLUSIONS: The data are consistent with BI and ivermectin interacting in teleost kidney tubules exclusively with p-glycoprotein, but not with one of the other known excretory transport systems. In addition, the studies demonstrate that freshly isolated functionally intact kidney tubules from killifish are a useful tool to differentiate the substrate specificity of renal transport systems with respect to drug elimination.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Ivermectin and onchocercal optic neuritis: short-term effects.

In 1982 the macrocyclic lactone, ivermectin, was first tested in human patients with onchocerciasis. It has since undergone phase I to IV trials and is now being widely distributed in onchocercal areas. The previous microfilaricide, diethylcarbamazine citrate (DEC), is known to precipitate or exacerbate active optic neuritis in some onchocercal patients, as part of a wider inflammatory response (the Mazzotti reaction). Ivermectin may also cause a mild reaction, especially in people with high microfilarial loads. Few data are available concerning the effect of ivermectin on active optic neuritis. A large, randomised, double-masked, phase IV trial is reported. Individuals were screened for evidence of optic nerve disease (OND), and those identified as possible cases of OND underwent detailed ophthalmic examination, including fluorescein angiography, before being dosed with ivermectin or placebo. A total of 6831 persons were screened of whom 856 (13%) underwent angiography prior to dosing. At 7-14 days after dosing an attempt was made to re-examine 50% of adults over the age of 20 years, including all those with OND. Six hundred and eighty-eight repeat or new angiograms were performed. During this period, 5 new cases of active optic neuritis and one case of exacerbation of existing optic neuritis were identified. Five of these individuals had received placebo and one ivermectin. Two individuals with optic neuritis before dosing had improved after 7-14 days. One had received placebo, the other ivermectin. Ivermectin does not appear to precipitate or exacerbate optic neuritis at a period of 7-14 days.

Adolescent↗
PubMed1999

Mass treatment with ivermectin for filariasis control in Papua New Guinea: impact on mosquito survival.

Field studies were carried out to determine the impact of mass human treatment with ivermectin on the survival of anthropophagic mosquitoes of the Anopheles punctulatus complex (Diptera: Culicidae), the vectors of lymphatic filariasis and malaria in Papua New Guinea. In a village where mass treatment had been given, using 400 microg/kg ivermectin plus 6 mg/kg diethylcarbamazine citrate (DEC), we performed pre- and post-treatment collections of freshly blood-engorged mosquitoes from the same nine bedrooms. All blood-fed mosquitoes collected less than 4 days after mass treatment died within 9 days, whereas 67% of those collected before treatment survived for >9 days. Comparison (using the log-rank test) of the survival curves for mosquitoes collected (i) before treatment, (ii)<4 days after treatment, and (iii) 28 days after treatment, showed the survival rate of group (ii) to be significantly lower than the other two (chi2=176, df=2, P<0.0001). Pre- and post-treatment all-night landing catches showed no reduction in human biting rates in the experimental village. In another village, where people were mass treated with ivermectin (400 microg/kg) only, the survival rates of freshly blood-engorged An. punctulatus collected from bedroom resting-sites less than 1 day after treatment, were compared to similar collections carried out at the same time in a nearby village where people were not treated with ivermectin. The 48-h survival rate for the ivermectin-treated village was 31% compared to 94% for the other; this difference was highly significant (chi2=32.42, df=1, P<0.0001). Mosquitoes fed 2 months post-treatment with DEC or collected 38 days post-treatment with ivermectin had normal survival rates. We conclude that the duration of the systemic lethal effect of ivermectin on mosquitoes is insufficient to be of epidemiological significance in filariasis control programmes that are based on biannual and annual single-dose treatments, but might reduce vectorial capacity sufficiently to block epidemics of dengue or even malaria.

Animals↗
PubMed1993

Effect of ivermectin on two filaria-vector pairs. Brugia malayi-Aedes aegypti; Litomosoides sigmodontis-Bdellonyssus bacoti.

The effect of ivermectin was studied on two filaria-vector pairs, Brugia malayi-Aedes aegypti and Litomosoides sigmodontis-Bdellonyssus bacoti. The rodent hosts, respectively Mastomys coucha and Meriones unguiculatus, were treated with ivermectin doses of 0.05 mg/kg, or 0.2 mg/kg or 2 mg/kg. Batches of vectors were fed on rodents, infected or not, treated or not, from H7 to D43 post-ivermectin. Vector survival was observed and dissections were performed to study the filarial development. It appears that ivermectin has no systemic effect on vectors, or very little. The drug acts on transmission because it affects the microfilariae. Transmission of L. sigmodontis is blocked because microfilariae are eliminated from the blood. Transmission of B. malayi is blocked although microfilaremia remains present at a low level. Two particular features are observed: microfilariae are hyper-ingested, but they do not cross the stomach wall (in contrast, they cross at a high rate in the control batch of Aedes, due to the "stomach wall limitation"). These events might be explained by a muscular passivity of the microfilariae treated with ivermectin. Transmission of the two filarioid species is restored normally about D25-40 post ivermectin because a new population of microfilariae has appeared. These ivermectin experiments emphasize the diversity and complexity of two important phases of the filarial cycle in the vector: the ingestion of microfilariae and the passage through the stomach wall.

Aedes↗
PubMed1999

Persistence of ivermectin in plasma and faeces following administration of a sustained-release bolus to cattle.

Six calves (weight 210 to 230 kg) were dosed with an intra-ruminal slow-release bolus prepared to deliver ivermectin at a low daily dosage for 135 days. Ivermectin concentrations in jugular blood 160 days post-treatment were determined by high performance liquid chromatography (HPLC) using fluorescence detection. Ivermectin plasma concentrations increased gradually to achieve the steady-state concentration (20 ng ml(-1)) at approximately four days post-treatment, which was maintained for 120 days. The ivermectin peak plasma concentration (28.5 ng ml(-1)) was attained at 15 days post-administration of the bolus. The faecal ivermectin concentration rose to a maximal concentration of 4.1 microg g(-1) at four days post-treatment, dropping to a steady-state concentration of around 1.18 microg g(-1) which was maintained up to 120 days post-treatment. Ivermectin was detected in both plasma (0.05 ng ml(-1)) and faeces (2.67 ng g(-1)) up to 160 days. The high levels of ivermectin recovered in faeces indicate that a large proportion of the dose released by the bolus (80 to 90 per cent) is excreted in faeces.

Animals↗
PubMed2001

Faecal excretion profile of moxidectin and ivermectin after oral administration in horses.

A study was undertaken to evaluate and compare faecal excretion of moxidectin and ivermectin in horses after oral administration of commercially available preparations. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups. Group I was treated with an oral gel formulation of moxidectin at the manufacturer's recommended therapeutic dose of 0.4 mg/kg b.w. Group II was treated with an oral paste formulation of ivermectin at the recommended dose of 0.2 mg/kg b.w. Faecal samples were collected at different times between 1 and 75 days post-treatment. After faecal drug extraction and derivatization, samples were analysed by High Performance Liquid Chromatography using fluorescence detection and computerized kinetic analysis. For both drugs the maximum concentration level was reached at 2.5 days post administration. The ivermectin treatment groups' faecal concentrations remained above the detectable level for 40 days (0.6 +/- 0.3 ng/g), whereas the moxidectin treatment group remained above the detectable level for 75 days (4.3 +/- 2.8 ng/g). Ivermectin presented a faster elimination rate than moxidectin, reaching 90% of the total drug excreted in faeces at four days post-treatment, whereas moxidectin reached similar levels at eight days post-treatment. No significant differences were observed for the values of maximum faecal concentration (C(max)) and time of C(max)(T(max)) between both groups of horses, demonstrating similar patterns of drug transference from plasma to the gastrointestinal tract. The values of the area under the faecal concentration time curve were slightly higher in the moxidectin treatment group (7104 +/- 2277 ng.day/g) but were not significantly different from those obtained in the ivermectin treatment group (5642 +/- 1122 ng.day/g). The results demonstrate that although a 100% higher dose level of moxidectin was used, attaining higher plasma concentration levels and more prolonged excretion and gut secretion than ivermectin, the concentration in faeces only represented 44.3+/- 18.0% of the total parental drug administered compared to 74.3 +/- 20.2% for ivermectin. This suggests a higher level of metabolization for moxidectin in the horse.

Administration, Oral↗
PubMed2000

Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine and albendazole, in various combinations.

Repeated, single, oral doses of combinations of ivermectin, diethylcarbamazine (DEC) or albendazole are recognized as important tools for parasite control in lymphatic filariasis. In order to assess the effects of re-treatment using these combinations in Brugia malayi infections, 40 asymptomatic microfilaraemics were re-treated at the end of the first year, with an additional, single, dose of the combination they had previously received. They were then followed-up for another year. The subjects, of both sexes and aged 14-70 years, each received a two-drug combination: ivermectin (200 micrograms/kg) with DEC (6 mg/kg); ivermectin (200 micrograms/kg) with albendazole (400 mg); or DEC (6 mg/kg) with albendazole (400 mg). The kinetics of microfilarial clearance were similar to that seen during the first treatment, the members of the two groups given DEC having less intense microfilaraemias, 1 year after the re-treatment, than those given ivermectin with albendazole (P < 0.001 for each comparison). At this time, the two DEC groups also had a higher proportion of amicrofilaraemic individuals (22 of 26) than the ivermectin + albendazole group (three of nine). There were fewer adverse reactions in all the groups after re-treatment than seen after the first treatment. In countries such as India, where there is no co-endemicity of onchocerciasis or loiasis, the options for control programmes in areas where brugian filariasis is endemic are DEC alone or DEC in combination with ivermectin or albendazole. Where there is no access to ivermectin, transmission control must be based on DEC alone or in combination with albendazole.

Adolescent↗
PubMed2001

Community-directed health (CDH) workers enhance the performance and sustainability of CDH programmes: experience from ivermectin distribution in Uganda.

The performance and 'drop-out' rates of ivermectin (Mectizan) distributors in the Ugandan programme for community-directed treatment with ivermectin (CDTI) were investigated and related to the manner in which the distributors were recruited. Distributors, from randomly selected communities endemic for onchocerciasis in seven of the 10 affected districts, were interviewed. Questionnaires were initially completed for 296 communities (in which ivermectin had been distributed in 1998 but not in 1999) and then extended to another 310 communities (in which ivermectin had been distributed in both study years). Discussions were also held with some other community members, in participatory evaluation meetings (PEM) in 14 communities from four districts. Despite the CDTI being labelled as 'community-directed', the first round of interviews and questionnaires revealed that there were in fact three categories of distributors: 322 (69.4%) of those questioned had been selected by community members and were therefore truly community-directed health workers (CDHW) but 101 (22%) were community-based health workers appointed by the leaders of the local council (CBHW-LC) and 41 (9%) were self-appointed volunteers (CBHW-SA). During 1999, only the CDHW received good community support; they still helped to mobilise and educate their community members and advocate CDTI, and 98% of them agreed that they would distribute ivermectin during the following year. In contrast, many of the CBHW-LC were neither supported nor appreciated by the community members. Presumably in consequence, many of the CBHW-LC did not help to mobilise or educate their community members in 1999, nor did they advocate CDTI. Almost all (95%) of the CBHW-LC said that they would not be available to distribute in the following year, and were therefore regarded as total 'drop-outs' from the CDTI. The CBHW-SA were better supported by community members than were the CBHW-LC, they did more to advocate the CDTI, and 93% reported that they would distribute ivermectin during the following year. The 'drop-out' rates for 1999 were < 2% for the CDHW, 7% for the CBHW-SA, and 95% for the CBHW-LC. The results also indicated that the CBHW-SA were not as reliable as the CDHW. Similar results were obtained from the second round of questionnaires, in which 224 (73%) of the interviewees were CDHW, 57 (18%) were CBHW-LC and 28 (9%) were CBHW-SA. The results of the PEM showed that the CDHW, who mainly came from the same kinship groups as the people who selected them, were likely to achieve higher ivermectin coverage within a week than the other categories of distributors. It is clear that, for the optimum performance and sustainability of the CDTI, the distributors used should be CDHW selected by their own community members.

Adolescent↗
PubMed1999

Treatment of the microfilaraemia of asymptomatic brugian filariasis with single doses of ivermectin, diethylcarbamazine or albendazole, in various combinations.

Several new chemotherapeutic tools are now available for the control of lymphatic filariasis. Combinations of single doses of antifilarial drugs are generally superior to single drugs. The efficacy and safety of albendazole in combination with diethylcarbamazine (DEC) or ivermectin, for the treatment of Brugia malayi infection, were investigated, for the first time, in an open, hospital-based study. Fifty-one asymptomatic microfilaraemics (with 108-4034 microfilariae/ml; median = 531) of both sexes and aged 14-70 years were randomly allocated to receive single-dose treatments of ivermectin (200 micrograms/kg) with diethylcarbamazine (DEC; 6 mg/kg), ivermectin (200 micrograms/kg) with albendazole (400 mg), DEC (6 mg/kg) with albendazole (400 mg), or albendazole (400 mg) alone. Albendazole alone had no effect on the microfilarial levels at the 1-year follow-up but both groups given DEC had significantly lower microfilaraemias (P < 0.015 and P < 0.02) than that given ivermectin with albendazole. Overall, 47%-64% of those given DEC but only 14% of those given ivermectin with albendazole appeared to be amicrofilaraemic 1 year post-treatment. The adverse reactions seen in the study were mild, transient and qualitatively similar to those seen earlier with ivermectin and DEC. The combination of DEC and albendazole, both well tested drugs, offers a new option for countries such as India where there is no onchocerciasis or loiasis and where ivermectin may not be immediately available. The direct and indirect effects of albendazole on intestinal helminths would be additional benefits.

Adolescent↗
PubMed1995

Knowledge, attitudes and practices during a community-level ivermectin distribution campaign in Guatemala.

Community acceptance and participation are essential for the success of mass ivermectin chemotherapy programmes for onchocerciasis (river blindness). To explore the local understanding of the purpose of ivermectin and willingness to continue taking the drug, we performed questionnaire surveys in four communities with hyperendemic onchocerciasis after each of three ivermectin treatment rounds. More than 100 respondents participated in each KAP survey, representing the heads of 30% of the households in each community. The respondents rarely stated that the goal of the ivermectin treatment programme was to prevent visual loss. Instead, they said they were taking the drug for their general well-being, to cure the onchocercal nodule (filaria), or to cure the microfilaria, a term newly introduced by agents of the treatment programme. The principal reason identified for refusal to take ivermectin was anxiety about drug-related adverse reactions, and there were marked differences between communities in acceptance of treatment. In one community over 50% of residents initially refused to take ivermectin, although participation rates improved somewhat after programmatic adjustments. We recommend that ivermectin distribution programmes establish surveillance activities to detect where acceptance is poor, so that timely and community-specific adjustments may be devised to improve participation.

Community Health Planning↗
PubMed2006

Ivermectin: uses and impact 20 years on.

PURPOSE OF REVIEW: Ivermectin was first discovered and used in veterinary medicine over 20 years ago. This review highlights some of the recent published research from 2005 through June 2006 on the use of ivermectin in both helminth and arthropod infection. RECENT FINDINGS: In recent years, several published studies have detailed the expanding role for ivermectin in multiple endo and ectoparasitic infections, including scabies, pediculosis, soil transmitted helminths, gnathostomiasis and myiasis. In addition, there is increasing experience with parenteral ivermectin for the treatment of disseminated strongyloidiasis. The success of ivermectin in reducing Onchocerca volvulus and Wuchereria bancrofti transmission through universal treatment in disease control programs continues to be well documented, but recent epidemiologic data describe suboptimal response to ivermectin by O. volvulus in a minority of individuals, the molecular markers for which are currently under investigation. SUMMARY: Over 20 years of research and clinical use have advanced ivermectin from its beginnings as a veterinary anthelmintic to its significant role in several successful disease control programs. Nevertheless, further research is needed to understand the basis for suboptimal response and to better define optimal drug regimens for varying diseases.

Animals↗
PubMed1996

Stability of ivermectin in rumen fluids.

To determine whether ivermectin is metabolized in the rumen, in vitro studies were conducted with the tritium-labelled H2B1a component of ivermectin in rumen fluid from sheep and cattle. No detectable metabolism occurred over 24 h in in vitro incubations at 38 degrees C. The viability of the microbes in the rumen fluids was demonstrated by the conversion of 17% and 11% of [14C]cellulose to 14CO2 in 24 h in the incubations with sheep and steer rumen fluids respectively. The results indicate that ivermectin is not metabolized in the rumen. Based on the lack of in vitro metabolism of ivermectin in rumen fluid, the similarity of in vitro liver microsomal metabolism with in vivo metabolism of the avermectins and the physicochemical properties of the avermectins, any disappearance of ivermectin in vitro from rumen fluid is probably a result of binding to solids or surfaces. Apparent discrimination by dung beetles, where observed, between control faeces and faeces from cattle or sheep treated with ivermectin or abamectin therefore must be attributable to chance, to factors unrelated to treatment or to factors such as changes in amino acid composition rather than the production of volatile metabolites of ivermectin.

Amino Acids↗
PubMed1996

Clinical and parasitological responses after up to 6.5 years of ivermectin treatment for onchocerciasis.

There are plans to use mass treatment with ivermectin to clear all Africa of the worst ocular and cutaneous effects of onchocerciasis. However, there remains uncertainty about the most suitable treatment regimen and the likely effects of ivermectin on onchocercal skin disease. We have followed 948 subjects for over 6 years in a double-blind, randomized, controlled study of ivermectin for onchocerciasis in a hyperendemic focus in Sierra Leone. Using an intention-to-treat analysis we found a microfilarial prevalence of 16% 6 months after up to 4 annual doses of ivermectin, and 13% prevalence in the group receiving up to 10 doses of ivermectin at 6-monthly intervals. Microfilarial loads were well suppressed in both groups, but repopulation data suggest that adult female worms are still alive and fecund, strongly underlining the need to continue treatment. A clear effect of ivermectin was demonstrated on itching, with about one-third of cases being alleviated. Significant reductions in the prevalence of serious hyperkeratosis, and possibly dyspigmentation (leopard skin), were noted, but not for any other onchocercal skin lesion. Six-monthly and annual treatment regimens with ivermectin were equally effective in terms of dermatological and parasitological impact.

Adolescent↗
PubMed1985

Efficacy of ivermectin against induced gastrointestinal nematode infections in goats.

The efficacy of ivermectin (0.08 per cent w/v oral solution) at different dose levels was evaluated against induced infections of adult Haemonchus contortus (21 days old) and Trichostrongylus colubriformis (21 days old) and fourth stage larvae of Oesophagostomum columbianum (17 days old), Ostertagia circumcincta (five days old) and Strongyloides papillosus (five days old). Twenty-five Boergoats (mutton goats) were randomly allocated by bodyweight within each sex to an untreated control group and four ivermectin treatment groups; ivermectin was administered at either 25, 50, 100 or 200 micrograms/kg orally, once. The goats were killed and processed for worm recovery 25 to 27 days after treatment. At 25 micrograms/kg the efficacy of ivermectin varied from 43 per cent for adult T colubriformis to more than 99 per cent for fourth larval stage O columbianum. Ivermectin at 50 micrograms/kg or higher was 99 per cent or more effective against all induced parasite infections with the exception of ivermectin at 50 micrograms/kg against S papillosus (97 per cent). For all parasites there was a statistically significant (P less than 0.05) difference between the control group and the pooled treated groups. No adverse reactions to ivermectin treatment were observed in the goats.

Animals↗
PubMed2002

Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects.

Safety and pharmacokinetics (PK) of the antiparasitic drug ivermectin, administered in higher and/or more frequent doses than currently approved for human use, were evaluated in a double-blind, placebo-controlled, dose escalation study. Subjects (n = 68) were assigned to one of four panels (3:1, ivermectin/placebo): 30 or 60 mg (three times a week) or 90 or 120 mg (single dose). The 30 mg panel (range: 34 7-594 microg/kg) also received a single dose with food after a 1-week washout. Safety assessments addressed both known ivermectin CNS effects and general toxicity. The primary safety endpoint was mydriasis, accurately quantitated by pupillometry. Ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-approved dose of 200 microg/kg. All dose regimens had a mydriatic effect similar to placebo. Adverse experiences were similar between ivermectin and placebo and did not increase with dose. Following single doses of 30 to 120 mg, AUC and Cmax were generally dose proportional, with t(max) approximately 4 hours and t1/2 approximately 18 hours. The geometric mean AUC of 30 mg ivermectin was 2.6 times higher when administered with food. Geometric mean AUC ratios (day 7/day 1) were 1.24 and 1.40 for the 30 and 60 mg doses, respectively, indicating that the accumulation of ivermectin given every fourth day is minimal. This study demonstrated that ivermectin is generally well tolerated at these higher doses and more frequent regimens.

Administration, Oral↗
PubMed2004

Long-term delivery of ivermectin by use of poly(D,L-lactic-co-glycolic)acid microparticles in dogs.

OBJECTIVE: To evaluate the potential utility of poly(D,L-lactic-co-glycolic)acid (PLGA) as a long-acting biodegradable drug delivery matrix for ivermectin used in the prevention of heartworm disease in dogs. ANIMALS: 30 adult female dogs. PROCEDURE: Microparticle formulations containing 25 weight percent (wt%), 35 wt%, and 50 wt% ivermectin were prepared by an oil-in-water emulsion technique with solvent extraction into excess water. A fourth formulation, consisting of a mixture of 15 wt% and 50 wt% ivermectin microparticles, was blended in a 1:1 ratio to result in a 32.5 wt% ivermectin formulation. Formulations were administered once on Day 0 to groups of 6 dogs at a dose of 0.5 mg of ivermectin/kg, s.c. Half of the dogs in each treatment group and 3 untreated control dogs were infected with Dirofilaria immitis larvae 121 and 170 days after treatment. Six months after infection, dogs were euthanatized and necropsies were performed. Pharmacokinetics and efficacy were investigated. RESULTS: Analysis of pharmacokinetic data revealed sustained release of ivermectin during at least 287 days in 3 distinct phases: a small initial peak, followed by release of drug through diffusion, and polymer degradation. Untreated control dogs were all infected with heartworms. Heartworms were not found in any of the dogs in the ivermectin-PLGA treated groups. Adverse clinical signs were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: All formulations were 100% effective in preventing development of adult heartworms. Results indicate that PLGA microparticles are a promising drug delivery matrix for use with ivermectin for the prevention of heartworm disease for at least 6 months after treatment.

Animals↗
PubMed2007

Bioavailability of a commercial formulation of ivermectin after subcutaneous administration to sheep.

OBJECTIVE: To evaluate bioavailability and other pharmacokinetic variables of a commercial formulation of ivermectin after IV administration to sheep. ANIMALS: 6 healthy adult sheep. PROCEDURES: A single dose of a commercial formulation of ivermectin (200 microg/kg) was administered IV to each sheep. After a washout period of 3 weeks, each sheep was administered ivermectin by SC injection. Plasma samples were obtained for up to 36 and up to 42 days after IV and SC administration, respectively. Ivermectin concentrations were quantified by use of high-performance liquid chromatography with fluorescence detection. RESULTS: Results obtained indicated that after IV administration, ivermectin is cleared slowly from plasma, tends to distribute and accumulate in the peripheral compartment, and is slowly eliminated from the body. After SC administration, noncompartmental analysis revealed that bioavailability of ivermectin is nearly complete (98.20%), has a slow mean absorption time of 0.96 days, and reaches a maximum plasma concentration of 19.55 ng/mL at 3.13 days. CONCLUSIONS AND CLINICAL RELEVANCE: The commercial formulation of ivermectin used in this study can be administered SC to sheep on the basis of a nearly complete bioavailability. In addition, the maximum plasma concentration and interval from SC injection until maximum plasma concentration is obtained are higher than those reported by other authors who used other routes of administration.

Animals↗
PubMed1990

Mortality and infertility in adult mosquitoes after the ingestion of blood containing ivermectin.

Mosquitoes of 3 species (Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus) were fed on human blood containing various concentrations of ivermectin. Three effects (death, decreased egg production, and reduced egg hatching) were observed in the insects, depending upon the concentration of ivermectin ingested. The LD50 of ivermectin in human blood for the 3 mosquito species was estimated to be 126, 208, and 698 ng/ml, respectively. Mosquitoes dying after ingestion of ivermectin developed signs of acute toxicity including paralysis, lethargy, incoordination, and difficulty in movement. Death usually occurred within 48-72 hr. With sublethal blood concentrations of the chemical, mosquitoes survived, but there was a marked reduction in both the number and viability of their eggs. This infertility was only temporary, however, as subsequent refeeding of the insects on uncontaminated blood resulted in the production of normal numbers of fertile eggs. Blood levels of ivermectin which made 50% of the eggs infertile in Ae. aegypti and Ae. albopictus were calculated 3.4 and 4.3 ng/ml, respectively. These latter concentrations of the chemical are within the range found in blood of humans and domestic animals receiving ivermectin for treatment of parasitic infections. This finding suggests that the widespread use of ivermectin in veterinary and human medicine may have an unrecognized effect on mosquito populations.

Aedes↗