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PubMed2004

An investigation of persistent microfilaridermias despite multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana.

If ivermectin-based programmes for the control of human onchocerciasis are to be successful, the drug must remain effective for as long as necessary. In an open, case-control study, an attempt was made to determine if the persistent, significant, Onchocerca volvulus microfilaridermias seen in some individuals who had received at least nine treatments with ivermectin were the result of the development of drug resistance in the parasite. Twenty-one of these 'sub-optimal' responders (cases) were matched, by age, weight, number of treatments, locality and skin microfilarial counts, with seven amicrofilaridermic responders and 14 ivermectin-naive subjects. The number of treatments taken, any potential drug interactions and significant underlying disease were determined from detailed clinical and laboratory studies. Each subject was treated with ivermectin during the study, so that plasma concentrations of the drug could be determined for 72 h from the time of dosage. The microfilarial and adult-worm responses to this treatment were assessed from skin microfilarial counts (obtained before the treatment and at days 8, 90 and 365 post-treatment), day-90 embryogrammes, and the results of fly-feeding experiments. Parasite-sensitivity criteria for various time-points were derived from earlier data on skin microfilaridermias and the effects of ivermectin on the adult worms. The results indicate that the significant microfilaridermias that persist despite multiple treatments with ivermectin are mainly attributable to the non-response of the adult female worms and not to inadequate drug exposure or other factors. The possibility that some adult female worms have developed resistance to ivermectin cannot be excluded. These results justify the routine monitoring of treatment efficacy in any ivermectin-based programme of disease control.

Adolescent↗
PubMed2005

Refusal to take ivermectin: the associated 'risk' factors in Hoima district, Uganda.

Community-directed treatment with ivermectin (CDTI), for the control of onchocerciasis, was launched in Uganda in 1997. In East Africa, as in other endemic areas, the refusal to take the drug reduces treatment coverage and therefore poses a serious threat to attempts to eliminate onchocerciasis as a disease of public-health importance. In early 2003, an attempt was therefore made to determine the factors associated with refusal to take ivermectin during mass treatment in 2002, by interviewing the individuals, from three Ugandan villages with CDTI, who had been eligible to receive ivermectin. The subject's socio-demographic characteristics, history of adverse reactions and participation in CDTI-related activities were explored, as potential 'risk' factors for refusing ivermectin in the treatment round in 2002. When odds ratios (OR) for refusal and their associated 95% confidence intervals (CI) were calculated, the villagers aged 18-35 years were found more likely to have received ivermectin in 2002 than their older counterparts (OR = 0.55; CI = 0.33-0.93). Individuals with an inter-current medical condition were also more likely to have received ivermectin in 2002 than the other villagers (OR = 0.56; CI = 0.32-0.99). Worryingly, the ingestion of ivermectin at any time before the 2002 treatment round was strongly associated with refusal to take ivermectin in that round (OR = 7.72; CI = 2.00-29.81), although there was no evidence that the adverse effects of treatment were significantly reducing coverage.

Adult↗
PubMed1993

Concurrent parasitic infections in onchocerciasis and the occurrence of adverse reactions after ivermectin treatment.

Ivermectin is a safe, effective, and relatively well-tolerated drug for the treatment of human onchocerciasis. However, due to side effects of the drug, large-scale ivermectin distribution without medical supervision is not recommended. The mechanisms involved in the pathogenesis of ivermectin-induced adverse reactions are not yet known. Since onchocerciasis patients are likely to have concurrent parasitic infections, we investigated whether side effects that occur after ivermectin treatment could be related to the presence of parasite eggs and cysts in stool samples prior to treatment. One hundred twenty-nine onchocerciasis patients were treated with a single dose of ivermectin (150 micrograms/kg) and side effects were graded according to the classification of Greene and others. Stool samples were collected before and three days after treatment. A high percentage (80.5%) of the patients reported adverse effects (57% mild, 14.1% moderate, and 9.4% severe reactions). Most (95.1%) of the patients had one or more concurrent parasitic infections. No relationship could be found between the occurrence and extent of side effects and the severity of concurrent intestinal parasitic infections. However, side effects were significantly correlated with pretreatment microfilarial counts. Ivermectin treatment did not induce significant short-term changes in Trichuris trichiura or Schistosoma mansoni egg counts. However, a significant reduction in Ascaris lumbricoides egg counts and Entamoeba coli cyst loads was observed; a cure rate of 46% for cysts was reached. In contrast, hookworm egg production increased after ivermectin treatment. Further studies are required to verify ivermectin-induced changes in cyst and hookworm loads as well as the significance of these findings.

Animals↗
PubMed1994

Ivermectin plus diethylcarbamazine: an additive effect on early microfilarial clearance.

The effects of ivermectin, diethylcarbamazine (DEC), and the combination of both drugs on levels of microfilaremia (mf) were studied in 30 male Polynesian Wuchereria bancrofti carriers. Microfilarial densities were measured 30 min (H1/2), 1 hr (H1), and 2, 4, 8, 24, and 96 hr (H2, H4, H8, H24, and H96) after supervised single doses of ivermectin plus DEC (400 micrograms/kg plus 1 mg/kg, respectively, 400 micrograms/kg plus 3 mg/kg, respectively, and 400 micrograms/kg plus 6 mg/kg, respectively), DEC (6 mg/kg) alone, and ivermectin (400 micrograms/kg and 100 micrograms/kg, respectively) alone given to six groups of five patients each. The results showed that 1) DEC alone or combined with ivermectin induced a rapid clearance of mf after drug intake; at H1/2, the number of circulating microfilariae was reduced to 16%, 8%, 28%, and 31%, respectively, of pretreatment values in the groups receiving ivermectin plus DEC (400 micrograms/kg plus 1 mg/kg, 400 micrograms/kg plus 3 mg/kg, and 400 micrograms/kg plus 6 mg/kg) and DEC (6 mg/kg) alone; 2) ivermectin alone induced a rapid increase of mf densities during the first 2 hr, followed by a sharp decrease from H4 to H96; and 3) between H8 and H96, mf clearance was almost complete with the combination of ivermectin and DEC. A comparison among groups did not show any synergistic interaction between ivermectin and DEC on the clearance of microfilaria, with the effect of each drug being additive to each another.

Animals↗
PubMed1996

Efficacy of ivermectin against nematodes infecting field populations of snowshoe hares (Lepus americanus) in Yukon, Canada.

From July 1990 to February 1991, nematode numbers in free-ranging snowshoe hares (Lepus americanus) at Kluane Lake, southwestern Yukon, Canada, were manipulated by subcutaneous injection (0.4 mg/kg) of ivermectin. Three field experiments were conducted to determine the degree of helminth loss associated with a single administration of ivermectin; the length of time that ivermectin was effective in reducing worm numbers; and the effect of repeated ivermectin administration in reducing worm numbers. Numbers of the nematodes, Protostrongylus boughtoni and Nematodirus triangularis were reduced by approximately 80% 2 wk after treatment with a single dose of ivermectin, and were still significantly lower than controls at 4 wk. However, beyond 2 wk, ivermectin did not affect the rate of acquisition of new worms of either species. All treated groups contained one or more hares in which numbers of P. boughtoni and N. triangularis were not reduced. In addition, ivermectin had no effect on numbers of Trichuris leporis or Passalurus sp. Overall, ivermectin was not as effective against the nematodes of free-ranging hares as has been reported for nematodes of domestic and laboratory animals.

Analysis of Variance↗
PubMedDate not supplied

[Detection of levamisole and ivermectin in organ samples from a dead collie].

A collie, known for its breed-dependent adverse reaction to ivermectin, was without any clinical signs. The dog was prophylactically treated with 3 mg/kg KG (s.c.) of levamisole. Within 15 minutes, the dog showed convulsions, vomitus, and dyspnea, and perished 2.5 hours after injection of the drugs. The pathological findings were not informative as to the cause of death, and with regard to the adverse reactions, additional application of ivermectin was not excluded. Therefore, organ samples were submitted for toxicological analysis of both levamisole and ivermectin. For detection of levamisole and ivermectin, modified GC/MS and HPLC procedures were developed. Concentrations up to 535 micrograms levamisole and up to 26 ng ivermectin were found per g tissue. Both analytical methods are sensitive enough to detect these drugs after application of low doses. This study elucidates that combination of low-dosed ivermectin and levamisole is no recommendable means against adverse effects of ivermectin, with respect to collies. Moreover, the synergistic effects of ivermectin and levamisole suggests the same drug incompatibility in other dog breeds and animal species.

Adipose Tissue↗
PubMed1984

Efficacy of ivermectin against the mange mite Sarcoptes scabiei var suis in pigs.

The efficacy of ivermectin administered by esophageal intubation in a single dose was evaluated against the mange mite Sarcoptes scabiei var suis in 24 naturally infested pigs. Six pigs were allocated to each of the 4 treatment groups. Control (group 1) pigs were given nonmedicated water, group 2 were given ivermectin at 300 micrograms/kg of body weight, group 3 were given ivermectin at 400 micrograms/kg, and group 4 were given ivermectin at 500 micrograms/kg. The pigs were examined for S scabiei before treatment and on days 7, 14, 21, and 28 after treatment. Of the 18 ivermectin-treated pigs, 10 had no live S scabiei recovered on day 7 after treatment, 16 had none on day 14, 18 had none on day 21, and 16 had none on day 28. All 6 nonmedicated control pigs had live S scabiei recovered on days 7 and 21, and 5 control pigs had mites on days 14 and 28. The single administration of ivermectin given by esophageal intubation was highly effective in reducing the number of S scabiei at all dose levels tested. The pooled ivermectin-treated groups had significantly (P less than 0.01) fewer mites than the control group on all posttreatment examination days. There were no statistically significant differences among the ivermectin dose levels.

Animals↗
PubMed1997

Demonstration of the sustained anthelmintic efficacy of a controlled-release capsule formulation of ivermectin in weaner lambs under field conditions in New Zealand.

Ten field trials were conducted in the North and South Islands of New Zealand to evaluate the anthelmintic efficacy and production responses attributable to treatment of weaner lambs with an intra-ruminal controlled-release capsule formulation of ivermectin. A total of 800 Coopworth, Perendale and Romney lambs weighing on average 20.8-34.8 kg were used. Lambs were either untreated or treated shortly after weaning with an ivermectin controlled-release capsule which delivers ivermectin at 0.8 mg per day for 100 days (minimum dose rate 20 microg/kg/day). Bodyweights, faecal nematode egg counts and dag scores (assessment of faecal soiling in the breech area) were determined before treatment and at about 4,8, 12, 14 and 16 weeks after treatment. Sheep treated with the Ivermectin capsule gained significantly more weight (11.6 kg) over the 16 weeks of the trials compared to untreated sheep (7.3 kg) (p < 0.01). Before treatment, faecal strongylid and Nematodirus spp. egg counts were equivalent (p > 0.10) but, at each time point thereafter, egg counts in ivermectin capsule-treated sheep were significantly lower (p < 0.01 or p < 0.05). Dag scores were not different at the start of the trial (p > 0.10), but at the end of the trial control sheep had significantly greater dags (p < 0.05) than sheep treated with the ivermectin capsule. These findings indicate that treated animals contributed significantly fewer nematode eggs to the contamination of pasture and therefore pasture contamination should be significantly reduced for at least 112 days. The productivity of the ivermectin capsule-treated sheep over the I6 weeks of the trials was also significantly increased compared to salvage-treated controls. Furthermore, the presence of dags, which predispose sheep to blowfly strike in the breech area and result in production losses due to the costs of dagging and downgrading of breech wool, were also significantly (p < 0.05) reduced in the ivermectin capsule-treated sheep.

Journal Article↗
PubMed1998

Elimination of an Infestation of Rat Fur Mites (Radfordia ensifera) from a Colony of Long Evans Rats, Using the Micro-dot Technique for Topical Administration of 1% Ivermectin.

Micro-dot delivery of 1% ivermectin was used in an effort to eliminate an infestation of rat fur mites (Radfordia ensifera) from a conventionally housed colony of Long Evans rats. The colony was used for breeding as well as for behavioral testing. A micropipette was used to apply a 1% solution of ivermectin (2 mg/kg of body weight) to the skin on the dorsal aspect of the shoulder. Three treatments were applied at approximately 2-week intervals. All rats in the colony were treated. However, to avoid toxicity to neonates, nursing females and their pups (control group) received mineral oil in lieu of ivermectin until after weaning, at which time they also were treated with ivermectin. During the treatment phase, skin scrapings were used to detect mites. Control rats remained positive for fur mites when treated with mineral oil. After 3 applications of ivermectin, all rats were found to be free of mites. During the posttreatment phase, skin scrapings, dorsal tape tests, and a washing method were performed on euthanatized rats to detect mites. Rats tested up to 129 days (18 weeks) after ivermectin treatment were still free of mites. In a breeding colony composed of rats of various sizes and ages, micropipette delivery of ivermectin allowed for accurate dosing to eliminate fur mites, while preventing inadvertent toxicosis. We did not detect obvious adverse effects on the breeding program or on the behavioral studies in which these rats were subsequently used, nor did we detect morbidity or mortality associated with ivermectin administration.

Journal Article↗
PubMed1999

Equivalent therapeutic efficacy and safety of ivermectin and lindane in the treatment of human scabies.

OBJECTIVE: To compare the therapeutic efficacy and safety of ivermectin and lindane for the treatment of human scabies. DESIGN: Randomized, prospective, controlled, double-blind, "double-dummy," and parallel clinical study. SETTING: A single department of dermatology at a hospital in Buenos Aires, Argentina. PATIENTS: Patients were outpatients, hospitalized patients, and those referred to our hospital from nursing homes and asylums. Fifty-three patients had clinical signs and symptoms compatible with scabies. INTERVENTION: Patients received either a single oral dose of ivermectin (150-200 microg/kg of body weight) or a topical application of 1% lindane solution. Treatment was repeated after 15 days if clinical cure had not occurred. MAIN OUTCOME MEASURES: Clinical healing and adverse effects. RESULTS: Of 53 patients, 43 (81%) completed the study, 19 in the group treated with ivermectin and 24 in the group treated with lindane. At day 15, 14 patients (74%; 95% confidence interval, 48.8%-90.8%) in the group receiving ivermectin showed healing of their scabies and 13 patients (54%; 95% confidence interval, 32.8%-74.4%) in the group treated with lindane were healed. At 29 days, both treatments resulted in statistically equivalent therapeutic efficacy: 18 patients (95%; 95% confidence interval, 74.0%-99.9%) were healed with ivermectin and 23 patients (96%; 95% confidence interval, 78.9%, 99.9%) were healed with lindane (P<.02). Adverse effects from the treatments were few, mild, and transient. Results from laboratory tests showed no major abnormalities and no difference between treatments. CONCLUSIONS: Ivermectin is as effective as lindane for the treatment of scabies. Ivermectin is simpler to use and, therefore, is a promising tool to improve compliance and to control infestations.

Adult↗
PubMed1990

Binding characteristics of ivermectin in plasma from collie dogs.

Two types of experiments were performed in an effort to demonstrate a role for plasma proteins in determining the amount of ivermectin available for transport across the blood-brain barrier of collie dogs sensitive to the effects of the compound. The solubility of ivermectin in plasma from non-sensitive and sensitive collies was measured and found to be identical at 100 micrograms/ml. An assay for measuring the low affinity binding interaction of ivermectin with plasma components was developed. The amount of ivermectin bound per unit of plasma was the same for samples from sensitive and non-sensitive dogs. Dog serum albumin and the high density lipoprotein portion of the plasma were both capable of binding ivermectin. No differences in the binding characteristics of ivermectin in plasma from ivermectin sensitive and non-sensitive collies were found.

Animals↗
PubMed1992

The distribution and some pharmacokinetic parameters of ivermectin in pigs.

Ivermectin was injected subcutaneously into five pigs at the usual dose rate of 300 micrograms/kg and found to distribute well to all tissues and body fluids which were sampled 24 h post-injection. Ivermectin was detected in the contents and mucus at all levels of the gastrointestinal tract. The drug was excreted in bile, with high concentrations of the drug in the intestines and faeces. High concentrations of ivermectin were measured in skin, ears and ear wax, suggesting that the drug should be effective in the treatment of ectoparasitic infestations, particularly ear mites. The high lipid solubility of the drug may explain the high concentrations found in ear wax and skin. Ivermectin was also detected in the body fluids and tissues of an untreated pig penned with the treated animals. Direct contact appeared to be necessary for transfer of ivermectin from the treated to the untreated pig but coprophagia or urine drinking is a possible explanation. The pharmacokinetics of ivermectin administered subcutaneously at a dose rate of 300 micrograms/kg to six pigs were studied. There was marked individual variation in the pharmacokinetics of ivermectin. In one pig the area under the plasma concentration-time curve was particularly high. This may reflect individual variation in uptake and excretion of the drug. The mean elimination half-life of the drug was 35.2 h, suggesting that the drug is cleared slowly from pigs with drug detectable in plasma for 6-10 days. This persistence should allow a short period of protection before re-infection with parasites.

Animals↗
PubMed1996

Effect of diet on the excretion profile of ivermectin in cattle faeces.

Two groups of 26 cattle (cross-bred, 3-8 years old, weight 450-650 kg) were placed onto 2 feed regimens, pasture-fed and grain-fed. The pasture-fed cattle were kept on irrigated pasture with hay supplement ad libitum, whereas the grain-fed cattle were kept in a feedlot and fed hay and lupin grain in a 40:60 ratio. Half the cattle within each feed group (n = 13) were given a subcutaneous injection of ivermectin (Ivomec) at the dose rate of 200 micrograms/kg liveweight. Over 5 times higher levels of ivermectin were excreted in the faeces of grain-fed cattle compared with pasture-fed (grazing) cattle. Peak excretion levels of 0.36 mg/kg (grain-fed) and 0.09 mg/kg (pasture-fed) of ivermectin were recorded at 6 and 8 days post-injection (dpi), respectively. Ivermectin was detected in faeces for up to 13 dpi (grain-fed) and 14 dpi (pasture-fed). Faecal pH in grain-fed cattle was more acidic (6.43) compared with pasture-fed cattle (7.28) and the levels of nitrogen in faeces from grain-fed cattle were higher (0.42%) compared with pasture-fed cattle (0.20%). Treatment with ivermectin had no influence on either the pH or nitrogen levels of faeces from either feed regimen. The impact of diet on the excretion profile of ivermectin is discussed in the context of studies attempting to demonstrate ecotoxic effects of ivermectin residues in cattle faeces on dung beetles.

Animal Feed↗
PubMed1986

A double-blind comparison of the efficacy and safety of ivermectin and diethylcarbamazine in a placebo controlled study of Senegalese patients with onchocerciasis.

Ivermectin (MK-933) has been compared with diethylcarbamazine (DEC) and placebo in a double-blind study in 30 adult male Senegalese patients with Onchocerca volvulus infection. 10 patients were randomly assigned to each treatment group. Ivermectin was administered as a single oral dose of 12 mg and DEC as 50 mg daily for two days and 100 mg twice daily for the following six days, total 1.3 g in eight days. Skin O. volvulus microfilaria densities remained near pre-study values in the placebo patients, but decreased rapidly with both active drugs to mean values about 2% of pretreatment (Day 8) and then increased slowly, reaching in 12 months about 4% of pre-treatment (ivermectin) and 18% (DEC). This difference is statistically significant. Clinical adverse reactions were recorded in four ivermectin, ten DEC and three placebo patients. One ivermectin and six DEC patients received steroid treatment for relief of these reactions. Serious adverse ocular changes were not seen in any patients, possibly because of the steroid therapy in the DEC patients. Adult O. volvulus from onchocercal nodules one and six months after treatment showed no effect of either drug on viability. Intra-uterine developing forms of the microfilariae appeared normal in all three treatment groups at the one month examination but deformed and degenerated forms were evident at six months in the ivermectin group but not in the DEC and placebo patients. Ivermectin as a single oral dose appears to be a safer and more effective microfilaricidal drug in human onchocerciasis than DEC in the standard multi-dose regimen.

Adolescent↗
PubMedDate not supplied

The effects of ivermectin used in combination with other known antiparasitic drugs on adult Onchocerca gutturosa and O. volvulus in vitro.

The effects of ivermectin at a concentration of 3.13 x 10(-6) M used in combination with other antiparasitic drugs on the viability of adult Onchocerca in vitro were assessed using MTT colorimetry and worm motility levels. When ivermectin was used against male O. gutturosa over a 7 d period in combination with suramin (5 x 10(-5) M), CGP 6140 (3.13 x 10(-6) M), CGP 20376 (1.95 x 10(-7) M), mefloquine (3.13 x 10(-6) M), levamisole (3.13 x 10(-6) M), mebendazole (5 x 10(-5) M), flubendazole (5 x 10(-5) M) and albendazole (5 x 10(-5) M), there was either no increased effect or only a marginally increased effect on motility levels when compared with the use of ivermectin alone. MTT colorimetry revealed that in most cases there was a cumulative effect of the 2 drugs used in combination but not a synergistic effect. In a trial extended to 26 d it was demonstrated that the combination of ivermectin and suramin did not produce a greater inhibition of motility than ivermectin alone. Using female O. volvulus, the activity of ivermectin, CGP 6140 and the 2 drugs combined was examined. The motility of all 3 groups exposed to drug(s) was suppressed by 24 h compared with controls. MTT colorimetry performed on day 7, using the pre-weighed anterior end of each worm, illustrated that ivermectin alone produced a 43.4% inhibition of formazan formation compared with controls, CGP 6140 alone produced 50.6% inhibition, while the drug combination produced a 72% inhibition, equivalent to the heat-killed control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Treatment of bancroftian filariasis in Recife, Brazil: a two-year comparative study of the efficacy of single treatments with ivermectin or diethylcarbamazine.

The effectiveness of single oral doses of ivermectin (200 or 400 micrograms/kg) and diethylcarbamazine (DEC, 6 mg/kg), preceded 4 d earlier by either placebo or very small doses of these drugs, was compared, over a 2-year period, in a double-blind trial in 67 microfilaraemic Brazilian men with bancroftian filariasis. Regimens containing ivermectin alone decreased the number of microfilariae significantly faster and more effectively for the first month after treatment than regimens containing DEC alone, but the latter were significantly more effective throughout the second year after treatment (1.7-8.2% of pretreatment levels with DEC vs. 12.6-30.8% with ivermectin during that period); the higher ivermectin dose showed a tendency towards more effectiveness than the lower dose. Most effective was the combination of ivermectin (20 micrograms/kg) followed 4 d later by DEC (6 mg/kg), with reduction of microfilaraemia to 2.4% of pretreatment levels at 2 years. Adverse reactions were well tolerated with all regimens, the reactions being significantly more generalized (i.e., fever) following ivermectin and localized (i.e., scrotal inflammatory nodules around dying adult worms) following DEC. Further trials of single-dose combination therapy vs. single high doses of ivermectin or DEC should determine the ideal regimen for treatment and control of bancroftian filariasis.

Administration, Oral↗
PubMed1993

Reduction in incidence of optic nerve disease with annual ivermectin to control onchocerciasis.

The safety and efficacy of ivermectin in the prevention of blindness from onchocerciasis have been established in many studies that have addressed the drug's effects on the front of the eye. We undertook a study with sufficient statistical power to detect an effect on optic nerve disease (OND), probably the main cause of blindness in the disorder. The trial was based in 34 mesoendemic communities in Kaduna State, Nigeria. Villagers aged 5 years and older were randomly assigned annual dosing with ivermectin or placebo for 3 years. Participants underwent medical and ophthalmological examinations before the first, third, and fourth treatments. 3522 villagers aged 15 and older were re-examined at least once. Skin-snip samples were taken at baseline for calculation of microfilarial load. The outcome measure was development of disc pallor accompanied by objective evidence of deterioration in visual function; 116 subjects (45 ivermectin-treated, 71 placebo-treated) showed such changes during the trial. The incidence rate ratio (ivermectin vs placebo) was 0.90 (95% CI 0.54-1.51) for subjects with loads of 0-10 mf (microfilariae) per mg skin and 0.52 (0.29-0.93) for subjects with more than 10 mf/mg. The incidence rate ratio varied little when account was taken of age, sex, presence of pre-existing disc pallor in one eye, previous use of diethylcarbamazine citrate, or doses of ivermectin or placebo received. There was evidence that ivermectin reduced the incidence of OND in subjects with microfilarial loads above 10 mf/mg but had little effect in those with lower loads. Sustained annual delivery of ivermectin could prevent a substantial proportion of onchocercal blindness in mesoendemic communities.

Adolescent↗
PubMed1993

Changes with time after treatment in the concentrations of ivermectin in fresh cow dung and in cow pats aged in the field.

An analytical procedure for detection of ivermectin in plasma samples was modified and used for measuring ivermectin concentrations in dung samples. The residues were quantified by high-performance liquid chromatography and fluorescence detection after extraction, purification, and derivatization into fluorescent reaction products. The concentrations of ivermectin in dung were measured after dosing heifers with 0.2 mg kg-1 by subcutaneous injection or 0.5 mg kg-1 by pour-on. Despite the 2.5 times higher pour-on dose, this formulation did not result in excretion of detectable concentrations of ivermectin over a longer period of time than did the injection treatment. Dung pats with ivermectin residues were exposed on grazing pastures until they were no longer colonised by flies and beetles. In the experiments performed under temperate and tropical conditions, the aging of the pats did not lead to a significant lowering of the concentrations of ivermectin. Flies or beetles colonising the pats some time after deposition may therefore not be exposed to decreased levels of ivermectin.

Administration, Topical↗