Environmental impact of ivermectin excreted by cattle treated in autumn on dung fauna and degradation of faeces on pasture.

The effect of ivermectin excreted in faeces of treated cattle on dung fauna and dung degradation on pasture during autumn was evaluated. Two groups of calves were used. One group was treated subcutaneously with ivermectin while the other remained as untreated control. Faeces deposited on 1, 3, 7, 14 and 21 days post-treatment (dpt) were removed on 1, 3, 7, 14, 21, 30 and 60 days post-deposition (dpd) and were used to determine the concentration of ivermectin and the percentage of organic matter and for the collection of colonising organisms. Samples from 1 and 3 dpt contained the highest drug concentration and percentage of organic matter compared to the control group (p<0.05). Faeces from the treated group showed lesser abundance and diversity of arthropods (p<0.05) than the control group. A reduction in numbers and diversity of dung fauna in faecal samples from treated animals was most remarkable at 1, 3 and 7 dpt, coinciding with the highest concentration of ivermectin and organic matter percentage.

The behaviour of doramectin in the gastrointestinal tract, its secretion in bile and pharmacokinetic disposition in the peripheral circulation after oral and intravenous administration to sheep.

Sheep were 'compartmentalized' by surgically implanting cannulae in the rumen, abomasum and terminal ileum with a re-entrant cannula inserted between the cystic duct and the duodenum to monitor bile secretion. Doramectin, containing a trace of [3H]-doramectin, was administered both intravenously (i.v.) and intraruminally (i.r.) at a dosage of 150 microg/kg. The pharmacokinetic behaviour of [3H]-labelled products was determined in these pools, and also in peripheral plasma, urine and faeces. Parent doramectin was also determined in plasma, abomasal digesta fluid and bile. Following i.r. administration, [3H] compounds were almost entirely associated with particulate digesta. A 14.5 h half-life in the rumen prolonged the presence of [3H] in the abomasum. Doramectin appeared to be degraded in abomasal digesta because only 24% of abomasal [3H] was attributed to the parent drug. Absorption of doramectin resulted in a systemic availability of 35%, of which 1.6 and 23.6% of the dose was contained in urine and biliary secretions, respectively. Following i.v. administration, almost negligible quantities of [3H] were secreted into the rumen or abomasum and only 2.7% of the dose was excreted in urine, whereas 132% was secreted in bile. This indicated that approximately one-third of biliary metabolites were enterohepatically recycled with biliary metabolites, elevating the proportion of [3H] in fluid digesta in the small intestine. Passage of the i.r.-administered drug through the gastrointestinal tract (GIT) resulted in virtually complete faecal excretion of [3H] within 5 days, whereas the continued secretion of i.v.-administered [3H] in bile prolonged the presence of [3H] in the GIT, with faecal clearance not being complete for at least 10 days. This multi-compartmental study has provided more information on the behaviour of doramectin than can be obtained from examining drug disposition in the peripheral circulation alone. With this knowledge, it is anticipated that opportunities for improving drug performance will be identified.

Determination of ivermectin in human plasma by high-performance liquid chromatography.

A specific reversed-phase HPLC-assay with sensitive fluorometric detection has been developed to measure the potent new antiparasitic agent ivermectin (CAS 70288-86-7) in human plasma (and urine). The lower limit of the method was 1 ng/ml and the intra-/interassay variability averaged 4.5/6.9%, respectively. The assay was applied for measuring plasma (urine) concentrations of ivermectin upto 56 (72 h) following a single oral dose of 6 and 12 mg. No unchanged or conjugated ivermectin could be detected in urine. Plasma concentrations increased linearly with dose but elimination half-life (12.6/13.4 h) was independent of the administered dose. Thus, the method is applicable for monitoring plasma levels during clinical and pharmacokinetic trials with ivermectin to evaluate its most efficacious dosage regimen.

Protein binding and ivermectin estimations in patients with onchocerciasis.

We measured ivermectin in plasma, urine, and saliva of nine patients with onchocerciasis. The aim was to establish pharmacokinetic parameters and to assess the most facile medium for use in monitoring compliance. Binding of ivermectin to plasma proteins in vitro was also investigated. The mean (+/- SEM) plasma values for the nine subjects were as follows: weight, 66.3 +/- 2.8 kg; dose, 11.11 +/- 0.4 mg; half-life, 56.50 +/- 7.01 hours; clearance, 142.5 +/- 22.6 L/kg; volume of distribution, 9.91 +/- 2.67 L/kg; area under the plasma concentration-time curve, 1545.3 +/- 190.5 ng/ml.hr; time to reach maximum concentration, 4.7 +/- 0.5 hours; and maximum concentration, 38.2 +/- 5.8 ng/ml. Ivermectin was not detected in the urine of any of the nine subjects. Low levels were found in saliva. Blood specimens remain the only reliable biologic fluid for assessment of compliance after ivermectin oral administration. Ivermectin binds specifically to human serum albumin.

[Possible effects on the environment of antibiotic residues in animal manure]. / Mogelijke effecten van antibiotica-residuen in dierlijke mest op het milieu.

After application to animals veterinary drugs can enter the environment faeces. Little is known about the impact these veterinary drugs can have on the environment. Antimicrobial drugs, ended up in the soil via manure, could affect microorganisms and thus disturb ecological cycles. A study of the literature on the impact on the environment of a number of important (groups of) antibiotics and an antiparasitic agent revealed that little is known about most of these agents.