Disposition of oxfendazole in goats and efficacy compared with sheep

The disposition of intraruminally administered oxfendazole (OFZ) in goats was studied at 5, 10 and 20 mg kg-1. The area under the plasma concentration with time curve (AUC) increased with increasing dose but at a declining rate. AUC was lower after intra-abomasal compared with intraruminal administration. OFZ was less effective against drug resistant Trichostrongylus colubriformis in goats than in sheep but was of similar efficacy against drug resistant Haemonchus contortus in both host species. In the same experiment peak plasma levels of OFZ in goats were about half those in sheep given the same dose. Of 70 goats tested in the field, total rumen bypass occurred in 12 per cent and partial bypass in 67 per cent. Lower systemic availability due to bypass would be expected to reduce further anthelmintic efficacy in goats. From the results of these experiments a dose rate of 10 mg kg-1 is recommended for goats. When given at this rate as a divided dose at 12 hourly intervals over 24 hours, OFZ was significantly more effective than a single dose in reducing egg counts.     

Efficacy of oxfendazole as administered by intraruminal injection to naturally infected calves

Oxfendazole, formulated into a 22.5% suspension, was administered by intraruminal injection to cattle at the rates of 0, 1.125, 2.25, 4.50, and 6.75 mg/kg of body weight. In total, 50 naturally infected calves were used, with 10 animals being allocated to each of the 5 treatment groups on the basis of pretreatment counts of nematode eggs per gram of feces. All animals were necropsied 7 days after treatment. The trial was done between December 1983 and January 1984, with the animals kept on concrete for a minimum of 35 days immediately before necropsy. For all nematodes and stages combined, efficacies were 97.4%, 98.8%, 99.5%, and 99.8% for oxfendazole at dosages of 1.125, 2.25, 4.50, and 6.75 mg/kg of body weight, respectively. Early 4th-stage larvae of Ostertagia and Nematodirus helvetianus adults were eliminated at rates greater than 93% only at the dosages of 4.50 mg/kg and above. Local or systemic adverse reactions were not observed in any of the animals.     

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.     

Bioequivalence in dogs of a meloxicam formulation administered as a transmucosal oral mist with an orally administered pioneer suspension product

Lees, P., Cheng, Z., Keefe, T. J., Weich, E., Bryd, J., Cedergren, R., Cozzi, E. Bioequivalence in dogs of a meloxicam formulation administered as a transmucosal oral mist with an orally administered pioneer suspension product. J. vet. Pharmacol. Therap.  36 , 78–84. A mucosal mist formulation of meloxicam, administered as a spray into the mouth (test article), was compared for bioequivalence to a pioneer meloxicam suspension for oral administration (reference article). Pharmacokinetic profiles and average bioequivalence were investigated in 20 dogs. The study design comprised a two‐period, two‐sequence, two‐treatment cross‐over design, with maximum concentration (C_max) and area under plasma concentration–time curve to last sampling time (AUC_last) used as pivotal bioequivalence variables. Bioequivalence of the products was confirmed, based on relative ratios of geometric mean concentrations (and 90% confidence intervals within the range 0.80–1.25) for C_max of 101.9 (97.99–106.0) and for AUC_last of 97.24 (94.44–100.1). The initial absorption of meloxicam was more rapid for the test article, despite virtually identical C_max values for the two products. Mean elimination half‐lives were 29.6 h (test article) and 30.0 h (reference article). The meloxicam plasma concentration–time profiles were considered in relation to published data on the inhibition of the cyclooxygenase‐1 (COX‐1) and COX‐2 isoenzymes by meloxicam.     

Anthelmintic efficacy of oxfendazole in calves

Oxfendazole, methyl [5-(Phenylsulfinyl)-1H-benzimidazol-2-yl]carbamate given to calves at dose level of 2.5 mg/kg as a paste, as a bolus, or as a drench resulted in excellent (97 to 100%) anthelmintic efficacy against mature Ostertagia ostertagi, Trichostrongylus axei, Cooperia oncophora, C mcmasteri, C pectinata, C punctata, Nematodirus helvetianus, Trichostrongylus longispicularis, Chabertia ovina, and Oesophagostomum radiatum. Against the early 4th stage larvage of O ostertagia and N helvetianus, these formulations had anthelmintic efficacies of 71% to 87% and 21% to 65%, respectively. As the result of differences in drug intake by individual calves, a pelleted feed additive given as top dress on chopped alfalfa hay gave an unsatisfactory mean anthelmintic response. Anthelmintic action in individual calves ranged from none to 98--100%.     

Immunity of calves treated with an oxfendazole pulse release bolus to challenge with Dictyocaulus viviparus

Two experiments were performed to study the effect of an oxfendazole pulse release intraruminal device (OPRB) on the development of lungworm infection and immunity in calves. Infections were monitored in OPRB-treated and control calves by faecal and pastural larval counts. Levels of immunity of grazing groups and helminth-free housed groups were compared by challenge infection. Even though signs of parasitic bronchitis were seen only in control animals, sufficient immunity had developed in OPRB-treated calves to prevent disease after a substantial challenge infection. However, the degree of immunity was less than in untreated grazing control groups and there were indications that it was related to initial infection levels. These results imply that the OPRB may successfully control parasitic bronchitis, provided that pasture larval infections are sufficient to allow the development of immunity.     

Delay in timing of the oxfendazole pulse release bolus in calves in The Netherlands

The efficacy of the oxfendazole pulse release bolus (OPRB) was tested in a grazing experiment at the University of Utrecht. Three groups of four OPRB-treated calves and one group of four untreated control calves were grazed on separate pastures between 18 May and 21 October 1987. Based on faecal egg counts for strongyle-type eggs and Nematodirus eggs, embryonation of Nematodirus eggs and faecal larval counts for lungworm, the first pulse of oxfendazole was released after 28 to 63 days, which was later than the period of approximately three weeks indicated by the manufacturer and others. As far as could be detected, the second to fifth pulses were not as delayed, but generally the three-week period was also exceeded. This delayed release of the pulse resulted in a build-up of pasture infectivity for gastrointestinal nematode larvae and lungworm larvae. Nevertheless, this did not result in clinical gastrointestinal helminthiasis and husk in the treated groups of calves, whereas severe husk and mild gastrointestinal helminthiasis were seen in the control group.     

Use of an oxfendazole pulse release bolus in calves exposed to natural subclinical infection with gastrointestinal nematodes

During the first grazing season a group of calves treated with an oxfendazole pulse release bolus achieved a mean (+/- sem) weight gain of 140.7 (+/- 6.7) kg compared with 106.5 (+/- 5.7) kg by a group treated once with ivermectin mid-season, and 116.9 (+/- 6.9) kg by a group which received no treatment. This economic advantage was maintained during the period of winter housing. By the end of the second grazing season, during which the animals received no anthelmintic medication, they weighed on average 20 kg more than the wholly untreated group, a difference which was not statistically significant. No signs of clinical disease were observed in either the animals dosed with a pulse release bolus or the undosed control animals during the two year trial period. The treatment with the oxfendazole pulse release bolus greatly reduced the degree of pasture contamination in the first year but in the second year those animals that had been treated in the first year developed higher worm egg counts (P less than 0.001) and thus augmented the levels of pasture contamination compared with the untreated control animals. Nematodirus battus and N filicollis both produced low grade but fertile infestations in the calves.     

Pasture study of two types of oxfendazole pulse release bolus for controlling nematodes in calves

One group of first-season calves was dosed with an oxfendazole pulse release bolus at spring turnout (April 30) and on July 15 a second group received the front-loaded oxfendazole pulse release bolus. The objective was to test the boluses for the prophylaxis or control of nematodiasis. The control group consisted of calves to which no bolus was administered. The three groups occupied separate but adjacent plots. For the first five weeks of the trial, three calves, artificially infected with Dictyocaulus viviparus grazed in each plot. Parasitic bronchitis severely affected the control calves, necessitating repeated emergency treatment, whereas administration of the bolus at turnout almost completely prevented this condition. D viviparus infection increased markedly on the control herbage in July and August but was eliminated by the end of June on pasture grazed by bolus treated calves. Treatment in mid-season with the front-loaded bolus brought an outbreak of parasitic bronchitis under control. Gastrointestinal worm egg output was satisfactorily suppressed after the administration of both boluses, resulting in reduced levels of herbage infection. Calves treated with a bolus at turnout gained significantly more weight than either the controls (P less than 0.001) or the calves treated with a front-loaded bolus in mid-season (P less than 0.01). The weight-gain of the calves treated with a front-loaded bolus was slightly but not significantly greater than that of the control calves. On the basis of faecal egg counts, the first pulse released from the standard boluses was delayed and one front-loaded bolus failed to release a dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Delay in timing of the oxfendazole pulse release bolus in calves in the Netherlands

Summary

The efficacy of the oxfendazole pulse release bolus (OPRB) was tested in a grazing experiment at the University of Utrecht. Three groups of four OPRB‐treated calves and one group of four untreated control calves were grazed on separate pastures between 18 May and 21 October 1987. Based on faecal egg counts for strongyle‐type eggs and Nematodirus eggs, embryonation of Nematodirus eggs and faecal larval counts for lungworm, the first pulse of oxfendazole was released after 28 to 63 days, which was later than the period of approximately three weeks indicated by the manufacturer and others. As far as could be detected, the second to fifth pulses were not as delayed, but generally the three‐week period was also exceeded.

This delayed release of the pulse resulted in a build‐up of pasture infectivity for gastrointestinal nematode larvae and lungworm larvae. Nevertheless, this did not result in clinical gastrointestinal helminthiasis and husk in the treated groups of calves, whereas severe husk and mild gastrointestinal helminthiasis were seen in the control group.     

The role of absorbed drug in the efficacy of oxfendazole against gastrointestinal nematodes

Comparisons were made of the relative efficacy of ozfendazole (OFZ), administered to sheep at 5 mg/kg either as an oral drench, single intravenous injection or 12 and 24 divided intravenous injections over 24 and 48 hours, against benzimidazole-resistanthaemonchus contortus andTrichostrongylus colubriformis. A single intravenous injection was at least equally potent as the oral drench whilst the divided dose intravenous regimes significantly increased OFZ efficacy against both parasite species.These findings demonstrate that (i) absorbed drug is important for the efficacy of OFZ against nematodes in the abomasum and small intestine and may be more important than unabsorbed drug passing down the gastrointestinal tract, and (ii) the maintenance of plasma OFZ levels of approximately 2 g/ml by divided dose regime increased efficacy compared with that achieved with the same total dose given as a single administration.     

The efficacy of oxfendazole against natural infections of nematodes & cestodes in sheep

Oxfendazole (5 mg/kg) was tested against natural infections of nematodes and cestodes in sheep in three experiments.

It was 100% effective against all stages of Ostertagia sp., Nematodirus spathiger, Oesophagostomum venulosum, Chabertia ovina, Moniezia expansa, immature 5th stage and adult Cooperia curticei and 4th stage Trichostrongylus sp. Efficacy was 99%–100% against immature 5th stage and adult Trichostrongylus sp., 67.8%and 91.6% against adult Strongyloides sp., 80.7%and 89.5% against immature 5th stage Trichuris ovis and 74% and 79% against Trichuris ovis.