Comparison of ivermectin, oxfendazole and levamisole for use as anthelmintics during the periparturient period in sheep.

Ewes synchronised with progestin impregnated sponges to reduce the spread of lambing were treated during the periparturient period with anthelmintic. The suppression of nematode egg output in faeces was measured in ewes given ivermectin either by subcutaneous injection or orally, or oxfendazole or levamisole orally. Ivermectin and oxfendazole reduced the output of eggs in the faeces of the ewes significantly (P less than 0.05) and the period of suppressed egg output was extended when ivermectin was given by subcutaneous injection. Plasma pepsinogen activity was estimated as a measure of abomasal damage. Pepsinogen values were significantly (P less than 0.001) lower in those animals treated with ivermectin by subcutaneous injection than in control animals. Levamisole showed a poorer response in terms of the output of eggs in faeces than either ivermectin or oxfendazole.

Comparison of the anthelmintic efficacy of oxfendazole or ivermectin administered orally and ivermectin administered subcutaneously to sheep during the periparturient period.

The suppression of nematode egg output in faeces was measured in ewes treated just before lambing with either oxfendazole or ivermectin by oral drench or with ivermectin by subcutaneous injection. Ivermectin and oxfendazole given orally were similarly effective, whereas ivermectin given by subcutaneous injection extended the period of suppressed egg output by about one week. The more persistent anthelmintic effect of ivermectin given subcutaneously was probably due to its extended half-life in the plasma of treated sheep. Plasma pepsinogen activity was less in the sheep given anthelmintic than in the untreated controls. Ivermectin caused a significantly greater reduction in pepsinogen activity than oxfendazole and was more effective when given subcutaneously than when given orally.

Pharmacokinetics of albendazole in man.

The pharmacokinetics of albendazole were investigated in healthy volunteers and in patients receiving albendazole for treatment of hydatid disease. Unchanged albendazole was below detectable limits in plasma, urine, bile and cyst fluid. The major metabolite present in all fluids was the sulfoxide. Maximum concentrations of albendazole sulfoxide in plasma were very variable, probably due to variable absorption of albendazole.

Albendazole--objective evidence of response in human hydatid disease.

Thirty-two patients with cysts caused by Echinococcus granulosus were treated with albendazole in a dosage of 10 mg/kg/day. Reversible abnormalities in liver-cell function tests were seen in five patients. Some radiological evidence of remission (on serial computed tomographic or ultrasound scanning) was seen in 15 of 22 patients undergoing a therapeutic course of albendazole (as opposed to those treated before or after surgery). In five patients, the cysts virtually disappeared. Apart from reduction in size, the appearance of a halo around the cysts and the apparent disappearance of daughter cysts has been seen. Serological findings have not correlated well with radiological or clinical improvement. Serum and cyst concentrations of albendazole sulfoxide (the principal metabolite) have been measured.

Effect of parasitism with Ostertagia circumcincta on pharmacokinetics of fenbendazole in sheep.

Plasma and abomasal fluid concentrations of fenbendazole and its two major metabolites in sheep experimentally infected with Ostertagia circumcincta were compared with those in the same sheep when non-parasitised. Bio-availability of the drug was reduced in the parasitised state. There was also a reduction in the proportion of drug present in the form of metabolites in parasitised as compared with non-parasitised animals.

Effect of feeding on the fate of orally administered phenylbutazone, trimethoprim and sulphadiazine in the horse.

Phenylbutazone, sulphadiazine and trimethoprim were administered to three horses on two occasions, recently fed and unfed, and the effect of feeding on the pharmacokinetics of the three drugs assessed. The mean peak concentrations of phenylbutazone and trimethoprim were reduced by feeding by 34 and 75 per cent, respectively. The pharmacokinetics of sulphadiazine were not significantly affected.

The binding and subsequent inhibition of tubulin polymerization in Ascaris suum (in vitro) by benzimidazole anthelmintics.

Benzimidazole anthelmintics may act by interfering with the microtubule system in Ascaris suum. Binding of benzimidazole anthelmintics, and their inactive metabolites, to A. suum tubulin was demonstrated by the inhibition of intestinal extracts of the nematode to bind [3H]colchicine. In addition, these compounds inhibited the polymerization of tubulin into microtubules in vitro.

The fumarate reductase system as a site of anthelmintic attack in Ascaris suum.

Various benzimidazole compounds have been shown to be highly effective as inhibitors (up to 50% reduction of activity) in vitro of the helminth-specific enzyme, fumarate reductase, of Ascaris suum. Anthelmintically active and inactive benzimidazoles were similarly effective as inhibitors of enzyme activity. Albendazole-induced inhibition of fumarate reductase was not observed when the enzyme was preincubated with NADH.

The pharmacokinetics of fenbendazole and oxfendazole in cattle.

The pharmacokinetics of fenbendazole and oxfendazole in cattle are described. The pharmacokinetics of oxfendazole were not significantly different when administered orally and by intra-ruminal injection. At a dose rate of 4.5 mg/kg, administered orally, fenbendazole gave rise to mean peak concentrations in plasma of fenbendazole and oxfendazole of 0.11 and 0.13 microgram/ml respectively. Oral administration of oxfendazole, at 4.5 mg/kg body weight, gave rise to plasma peak concentrations of fenbendazole and oxfendazole of 0.10 and 0.20 microgram/ml respectively. Following intra-ruminal administration of oxfendazole, the peak concentrations were 0.11 and 0.18 microgram/ml respectively.

Pharmacokinetics of levamisole in sheep.

Levamisole, at a dose rate of 7.5 mg/kg, produced mean peak plasma concentrations of 3.1, 0.7 and 0.8 microgram/ml in four sheep after administrations by the subcutaneous, oral and intraruminal routes respectively. The mean peak concentrations in abomasal fluid were 33, 164 and 21 micrograms/ml respectively. The bioavailability of levamisole to the systemic compartment was less after oral and intraruminal administration than after subcutaneous administration. In six sheep there were no significant differences in the plasma concentrations obtained after subcutaneous administration in the thoracic, neck or gluteal regions. Dividing the dose between five sites in the gluteal region produced higher peak plasma concentrations than when injected into a single site.

Pharmacokinetics of oxfendazole in sheep.

Pharmacokinetics of oxfendazole and its sulfone metabolite were determined in 6 sheep. Oxfendazole achieved mean peak plasma concentrations of 0.76 micrograms/ml at 30 hours after oral administration of oxfendazole (10 mg/kg of body weight), and concentrations were detectable for up to 7 days after administration. Mean peak abomasal concentrations of 3.55 micrograms/ml occurred 20 hours after administration and were detectable up to 9 days after administration. Concentrations of sulfone in plasma and abomasal fluid were generally lower than were those of oxfendazole.

Pharmacokinetics of fenbendazole in sheep.

Concentrations of fenbendazole and its sulfoxide, oxfendazole, and sulfone metabolites were determined in 6 sheep after oral administration of fenbendazole (10 mg/kd of body weight). Mean peak concentrations in plasma of fenbendazole, oxfendazole, and sulfone of 0.15, 0.29, and 0.17 micrograms/ml occurred 24, 30, and 36 hours after administration, respectively. Mean peak concentrations in abomasal fluid were 1.82, 0.66, and 0.07 micrograms/ml occurring at 30, 48, and 72 hours, respectively. Fenbendazole and oxfendhzole were detectable in plasma and abomasal fluids for 5 days after administration. Much of the anthelmintic activity of fenbendazole may be due to the oxfendazole metabolite. Plasma concentrations of fenbendazole were less and persisted for a shorter period after intra-abomasal administration than after oral administration.