E. W. Scott

The distribution and some pharmacokinetic parameters of ivermectin in pigs.

Ivermectin was injected subcutaneously into five pigs at the usual dose rate of 300 µg/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 µg/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.

Effect of parasitism with Nematodirus battus on the pharmacokinetics of levamisole, ivermectin and netobimin

The pharmacokinetics of levamisole, ivermectin and netobimin administered orally and by subcutaneous injection were compared in lambs exposed to a moderate challenge with Nematodirus battus and in parasite naive lambs. There were no significant differences (P greater than 0.05) in the bioavailability of any of the anthelmintics tested between parasitized and non-parasitized animals. Levamisole reduced nematode faecal egg output by more than 99% when administered by either route. Ivermectin was also highly effective (greater than 99%). Orally administered netobimin reduced egg output by more than 98% seven days after administration. However egg output was only reduced by 89% 21 days after administration, suggesting poor activity against the early parasitic stages of N. battus. Netobimin was not effective against N. battus when administered by the subcutaneous route and this was probably because very low plasma concentrations of its active albendazole metabolites were achieved.

Level of Benzimidazole resistance in a strain of Ostertagia circumcincta studied over several infections in lambs

A benzimidazole-resistant strain of Ostertagia circumcincta (HFRO) was used experimentally to infect lambs. The level of resistance, measured by an egg hatch assay, was studied throughout each infection and also after treatment of the lambs with fenbendazole. The HFRO strain was highly resistant to benzimidazoles. There was day-to-day variation in the level of resistance throughout a single infection with a high level of resistance in the early part of the infection, around Day 27 post-inoculation of infective larvae, falling to a lower level later in the infection. Egg hatch assays on the 3 days immediately post-treatment with fenbendazole showed the resistance level was high then resistance fell to the pre-treatment level after 7 days. Selection for benzimidazole resistance using fenbendazole treatment at the normal dose rate of 5 mg kg-1 over five passages of the HFRO strain in lambs failed to increase the resistance level. Storage of larvae over a 5-month period at 4 degrees C, prior to infection of lambs, did not produce any alteration in the resistance level. The possible reasons for the variations in resistance found with the HFRO strain are discussed along with the implications for sheep parasite control and further development of benzimidazole resistance.