The efficacy of oxfendazole administered as a bolus compared with a drench formulation

Summary

In a flock of 40 ewe lambs of the Texel breed the anthelmintic oxfendazole was tested in two different formulations, a 2.265 per cent suspension and a 4 gram bolus containing 151 mg active ingredient. All treatments were based on a dose rate of 5 mg / kg body weight. Faecal examinations and larval differentiations were carried out on the day of treatment and two and seven days later. No differences in efficacy were apparent between the two treated groups.

Oxfendazole in either formulation was 100 per cent effective in removing the major strongylids and trichostrongylids.

A lower activity was seen against Strongyloides papillosus.     

Evaluation of the efficacy of oxfendazole against larval and adult Toxascaris leonina in the dog

The efficacy of oxfendazole, given at a dose rate of 10 mg/kg for three consecutive days, against adult and larval Toxascaris leonina was determined in four litters of naturally infected adolescent greyhounds. When administered to five dogs 10 weeks after exposure to infectiori, oxfendazole gave an efficacy value of 100 per cent as determined by comparison of the numbers of adult worms expelled and the numbers remaining at subsequent post mortem examination. When medication was given only five weeks after exposure to infection, the number of immature T. leonina in 10 treated pups was found to be reduced by 92-1 per cent as compared with 10 matched, untreated controls. Incidental infections of Toxocara canis and Uncinaria stenocephala were adequately controlled but the treatment was less effective against Trichuris vulpis and Strongyloides species.     

Efficacy of oxfendazole against inhibited larvae of Ostertagia ostertagi in naturally infected calves in the southern USA

Forty yearling calves were assigned to four equal groups; three of the groups were treated with oxfendazole at dose rates of 6.75 mg/kg, 4.50 mg/kg, or 2.25 mg/kg bodyweight while the fourth group served as an untreated control. The calves were native to north-east Mississippi, USA, and harboured natural infections of gastrointestinal nematodes. The study was conducted during July when inhibited early fourth-stage larvae may be found in large numbers after their acquisition in the spring. The calves were maintained in separate groups on concrete-floored pens for 17 days before the intraruminal administration of oxfendazole. Seven days after treatment, the calves were slaughtered and the gastrointestinal parasites counted. At all the dose rates examined oxfendazole exhibited an efficacy of at least 99.4 per cent against adults of Haemonchus placei, Trichostrongylus axei, Bunostomum phlebotomum, Cooperia species, T colubriformis, Oesophagostomum radiatum, and Trichuris ovis. The efficacy against adult Ostertagia ostertagi was at least 99.4 per cent at dose rates of 6.75 and 4.50 mg/kg bodyweight, but decreased to 93.7 per cent at 2.25 mg/kg. The efficacy of oxfendazole against inhibited larvae of O ostertagi decreased with dose rate from 78.8 per cent at 6.75 mg/kg, to 58.9 per cent at 4.50 mg/kg and 20.3 per cent at 2.25 mg/kg bodyweight.     

An evaluation of the efficacy of oxfendazole against the common nematode parasites of the horse.

In a controlled trial in naturally-infected young ponies, oxfendazole administered orally at dose-rates of 10 mg per kg and 50 mg per kg resulted in complete elimination of Trichostrongylus axei, Parascaris equorum, Oxyuris equi and adult Strongylus vulgaris. Also, all migrating Strongylus edentatus larvae recovered from the subperitoneal tissues of the flank were found to be dead. Minimum efficiencies of 99.8 per cent and 99.1 per cent were obtained against adult small strongyles (Trichonema spp) and 97.6 per cent and 100 per cent of developing small strongyle larvae at dose-rates of 10 mg per kg and 50 mg per kg respectively. Although the arterial lesions caused by migrating S vulgaris larvae were less severe in the treated compared with the untreated animals, reductions in mean larval numbers over controls were only in the region of 49 to 59 per cent.     

Efficacy of ivermectin against benzimidazole-resistant nematodes of sheep

Two trials involving a total of 36 Dorset horn lambs were conducted to assess the anthelmintic efficacy of ivermectin against experimental infections of benzimidazole-resistant strains of Haemonchus contortus and Ostertagia circumcincta. Two resistant strains of each of the two species were used and in each trial the lambs were allocated to three groups. One group was given 200 micrograms ivermectin/kg bodyweight orally, the second group was given 5 mg oxfendazole/kg bodyweight orally and the third group remained untreated as controls. Fourteen days after treatment the lambs were necropsied. Ivermectin was found to be more than 99 per cent to 100 per cent effective against all four benzimidazole-resistant strains, whereas oxfendazole was 78.6 per cent and 83.8 per cent effective against the H contortus strains, and 25.6 per cent and 39.8 per cent effective against the O circumcincta strains.     

Evaluation of the efficacy of oxfendazole against larval and adult Toxocara canis in unweaned dogs

The efficacy of oxfendazole given at a dose-rate of 10 mg kg^-1 for 3 consecutive days against adult and larval Toxocara canis was determined in four litters of naturally infected unweaned greyhound pups. Comparison of the worm-burdens of four pups treated on days 30–32 post partum with four matched litter-mate untreated controls gave an apparent efficacy value of 98-5 per cent, the numbers of adult T. canis at post mortem examination being 3 and 202, respectively. A similar comparison involving 10 pups treated on the 5th to 7th days of life, when the T. canis would have been in various stages of larval development, gave an overall efficacy value of 75.8 per cent, with worm-counts of 1,325 and 321 for control and treatment groups. However, a greater reduction (84.1–91.7 per cent) was observed in worms achieving a length of 40 mm by the time of post mortem examination (Day 21 post partum) than in shorter worms. In the latter case, no demonstrable anthelmintic activity was detected.     

Evaluation of oxfendazole against natural infections of gastrointestinal nematodes in Nigerian calves

The efficacy of oxfendazole was tested in naturally infected Sokoto-Gudali calves at a dosage of 2.8 mg per kg. At this dosage level, oxfendazole showed 100 per cent efficacy against adult and immature forms of Haemonchus spp, Trichostrongylus spp, Bunostomum phlebotomum and Oesophagostomum radiatum. Although efficacy of 100 per cent was recorded for the adult form of Cooperia spp, only 48 per cent reduction was recorded for its immature stages. Similarly, a percentage reduction of 75 was recorded for adult Trichuris spp. No larvae hatched out of a seven-day vermiculite culture of faeces collected from the treated calves 24 h after treatment.     

Controlled trials of the anthelmintic oxfendazole in ewes and lambs naturally infected with gastrointestinal nematodes.

Oxfendazole doses at a rate of 5 mg per kg, before or after lambing, reduced nematode egg output to insignificant levels in ewes, most of which were not exposed to re-infection. Ewes treated with oxfendazole had a significantly lower egg output than those treated with levamisole, although the latter anthelmintic was also highly effective. In lambs, oxfendazole at a dose rate of 5 mg per kg, showed 100 per cent efficacy for Ostertagia circumcincta, O trifurcata, Teledorsagia davtiani, Trichostrongylus axei, T vitrinus, T colubriformis, Nematodirus battus, N filicollis, immature Nematodirus, Chabertia ovina, and 93 per cent efficacy for Trichuris spp. Levamisole showed similar efficacies but did not remove Trichuris.     

Disposition of fenbendazole in the rabbit

The disposition of fenbendazole was studied in rabbits following either oral or intravenous administration. The major metabolites appearing in plasma were fenbendazole sulphoxide (oxfendazole) and fenbendazole sulphone. Calculation of the total urinary and faecal elimination of the drug and of its known metabolites showed that only 40 per cent of the dose was recovered after oral dosing; 29.7 per cent after an intravenous dose. The sulphoxide and sulphone were minor elimination products. The major excretory metabolite was p-hydroxyfenbendazole.     

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.     

Comparison of early season suppressive anthelmintic prophylactic methods for parasitic gastroenteritis and bronchitis in calves

A comparison was made of the material costs and effectiveness of three methods of early season suppression by anthelmintic medication of Ostertagia species and two of Dictyocaulus viviparus in calves, each method suppressing faecal egg output for different lengths of time from the start of spring grazing. The anthelmintics used were: Morantel bolus administered five days before going to grazing; oxfendazole given three times at three, six and nine weeks after the start of grazing and ivermectin injected three, eight and 13 weeks after going to pasture. The effectiveness of each was estimated by comparison with worm numbers in untreated control calves. Oxfendazole, which was active for the shortest time (about 65 days) from the start of grazing (May 1), produced a 78.1 per cent reduction in Ostertagia species and an 84.4 per cent reduction in D viviparus. The morantel bolus was estimated to be active for 90 days and resulted in a 94.3 per cent reduction of Ostertagia species. The ivermectin treatment, which, because of the prolonged excretion of the chemical and different sensitivity of worm species, was estimated to suppress Ostertagia species for 105 days and D viviparus for 119 days, caused reductions of 98.7 per cent of the former and 97.4 per cent of the latter species. Material costs per calf were estimated at pounds 1.25 for oxfendazole, pounds 2.00 for ivermectin and pounds 10 for the morantel bolus.     

Evaluation of oxfendazole against natural infections of gastro-intestinal nematodes and lung-worms in calves.

The anthelmintic activity of oxfendazole (Syntex) was tested in calves at dosages of 2-5 and 5-0 mg per kg. At both dose levels, oxfendazole showed 100 per cent efficacy against adult Ostertagia ostertagi, O lyrata, O cremensis, fifth stage Ostertagia spp and adult Haemonchus spp. Against adult Cooperia oncophora, efficacy was 99.8 per cent and 100 per cent at doses of 2.5 mg per kg and 5.0 mg per kg respectively while at both dose levels 100 per cent activity was recorded against C surnabada and fourth and fifth stage Cooperia spp. One hundred per cent efficacy was obtained with both dose levels against adult and fifth stage Dictyodaulus viviaprus; against Trichuris spp, percentage efficacy was 92 and 100 per cent at doses 2.5 and 5.0 mg per kg respectively. Oxfendazole showed higher efficacy than levamisole against Ostertagia spp but against the other species encountered, both anthelmintics possessed similar efficacy. Both anthelmintics significantly increased the calves' weight gains.     

Responses in milk production to the control of gastrointestinal nematode and paramphistome parasites in dairy cattle

Objective To determine the effect of treating naturally acquired gastrointestinal nematode and paramphistome infections on milk production in dairy cattle.
Design A field trial.
Animals One thousand two hundred and thirty nine dairy cows.
Procedure Cows were either not treated or treated with 4.5 mg/kg oxfendazole, 16.6 mg/kg oxyclozanide or 4.5 mg/kg oxfendazole and 16.6 mg/kg oxyclozanide in March, May and August.
Results A significant increase in milk production, averaging 0.4 L (SE 0.2) per day, was seen when dairy cows infected with gastrointestinal nematodes and paramphistomes were treated with oxfendazole or oxfendazole and oxyclozanide in March, May and August. Cows treated with oxyclozanide alone at these times produced no more milk than untreated cows.
Faecal egg counts confirmed that oxyclozanide treatment reduced paramphistome populations and oxfendazole treatment reduced nematode populations in cows over the 7-month monitoring period.
Conclusion When dairy cows infested with gastrointestinal nematodes and paramphistomes were treated with oxfendazole alone or oxfendazole and oxyclozanide in March, May and August milk production increased.     

Errata

Summary

Netobimin was tested for efficacy against Haemonchus contortus using 7 groups of 5 parasite‐free lambs of six month age. The lambs in group 1 and 2 were infected with 10,000 larvae of a benzimidazole susceptible strain and those in groups 3–7 with the same dose of a resistant strain. The following treatment scheme was applied 21 days after infection: lambs in groups 2 and 4 ‐ 7.5 mg kg^‐1 netobimin, in group 5 ‐ 20 mg kg^‐1 netobimin, in group 6 ‐ 5 mg kg^‐1 oxfendazole and in group 7 ‐ 3.8 mg kg^‐1 albendazole. The lambs in groups 1 and 3 remained untreated. All lambs were slaughtered 28 days after infection. Egg counts decreased in all lambs after treatment, but increased again in lambs in groups 4, 6 and 7. There was a slight increase in lambs in group 5, while those in group 2 remained negative. Post‐mortem worm counts showed a reduction of 99.8 per cent in lambs in group 2 compared to those in group 1. In lambs in group 4–7 the reduction of worm counts was respectively 40.9, 89.5, 24.7 and 40.7 per cent compared to those in group 3. Egg development assays carried out 20 days after infection showed an average LD₅₀ of 0.46 mg ml^‐1 thiabendazole for the resistant strain. After treatment (day 27) the LD₅₀ was 0.53, 0.48, 0.58, 0.56 and 0.47 in lambs in the groups 3–7. It is concluded that netobimin and other (pro) ‐benzimidazoles should not be used in cases of benzimidazole resistance and that levamisole, pyrantel tartrate or ivermectin are preferable.     

Field trial of the efficacy of dicyclanil for the prevention of wohlfahrtiosis of sheep

Two groups of 40 ewes from each of two flocks were used in a field trial of the efficacy of dicyclanil to protect them against a natural infestation by Wohlfahrtia magnifica larvae, when administered topically as a spray-on formulation. The animals of one group in each flock were treated with dicyclanil and those of the other group were left untreated as controls. The trial lasted 31 weeks and the animals were inspected daily for wohlfahrtiosis. The incidences of wohlfahrtiosis ranged from 17.5 per cent to 20 per cent in the control groups and from 2.5 per cent to 5 per cent in the treated groups, and 77.8 per cent of the infestations were in the genitalia. When compared with the control groups, dicyclanil achieved a 100 per cent reduction of infestation in the treated groups of both flocks for at least 24 weeks, and an 80 per cent reduction for 31 weeks.     

Comparison of vedaprofen and meloxicam in dogs with musculoskeletal pain and inflammation

In this randomised, multicentre clinical study, dogs with musculoskeletal pain and inflammation were treated with either vedaprofen or meloxicam administered orally at the recommended dose rates. Clinical examinations were carried out regularly and clinical severity scores assigned. In total, 214 cases (73 acute, 141 chronic) were evaluated. Treatment with vedaprofen and meloxicam was continued for 14 and 17 days, respectively, in the acute cases, and 38 and 39 days in the chronic cases. NSAID treatment resulted in a significant improvement in clinical scores. The overall response to treatment ('responders') at the final clinical examination was 89 per cent and 87 per cent in the acute cases and 72 per cent and 65 per cent in the chronic cases in the vedaprofen and meloxicam groups, respectively. Mild transient gastrointestinal signs were observed in both groups (11 per cent vedaprofen, 12 per cent meloxicam). Adverse effects related to NSAIDs resulted in treatment cessation in 5 per cent of the dogs in each group. Vedaprofen and meloxicam were efficacious in, and well tolerated by, most of the dogs in the study.     

Field studies of the immunisation of lambs with drug-abbreviated infections of Trichostrongylus colubriformis and Ostertagia circumcincta

Fifty, 5–6 month-old lambs were randomly allocated to five equal groups. Three groups of lambs were immunised by three oxfendazole-abbreviated (artificial) infections of Trichostrongylus colubriformis and Ostertagia circutncincta. Group 1 was immunised with a high dose of larvae, Group 2 with a medium dose and Group 3 with a low dose. A fourth group was treated with oxfendazole only and a fifth group was not treated (control). All groups were grazed together on pasture naturally contaminated with nematode larvae. Immunisation significantly reduced the number of eggs per gram of faeces in all three groups, but the lowest faecal egg count was seen in Group 3 (immunised with the lowest number of larvae). Significantly better liveweight gains and wool weight were observed in Group 2 animals than in the control group. Of all anthelmintic-treated animals, only Group 1 lambs did not have a signscantly lower dag weight than controls.     

Remission of the clinical signs of atopic dermatitis in dogs after cessation of treatment with cyclosporin A or methylprednisolone

Seventy-eight dogs with atopic dermatitis were treated for four months with either cyclosporin A or methylprednisolone. During the two months after the treatment ceased, 87 per cent of the dogs treated with methylprednisolone relapsed after a mean period of 27.9 days, whereas only 62 per cent of the dogs treated with cyclosporin A relapsed after a mean period of 40.7 days (P < .0.001). The clinical condition of the dogs was evaluated either when they relapsed, or two months after the treatment ceased if they had not relapsed. Both the skin lesions and pruritus increased significantly more markedly in the dogs treated with methylprednisolone than in those treated with cyclosporin A. At the end of the study the skin lesions were markedly less severe than before the therapy; in the dogs in both groups that did not relapse, the lesion score was improved by 77 per cent two months after the treatment had stopped, and in the dogs that did relapse the lesion scores had improved by 45 per cent and 35 per cent in the dogs treated with cyclosporin A and methylprednisolone, respectively. Pruritus remained well controlled in the dogs that did not relapse, but increased to baseline levels or close to baseline in the dogs that relapsed.     

Comparison of the effects of oral or subcutaneous carprofen or ketoprofen in rats undergoing laparotomy

Rats undergoing laparotomy received either carprofen (5 mg/kg) or ketoprofen (5 mg/kg) administered orally in flavoured gelatin, or by subcutaneous injection. A control group that received no analgesic showed a significant (3 per cent) fall in bodyweight (P = 0.009) after laparotomy. This decrease was greater than that seen in the groups receiving carprofen (P = 0.006) or ketoprofen (P = 0.012) administered subcutaneously, which continued to gain weight following surgery. All animals showed a significant fall in food consumption but this decrease was greater in the jelly alone group (47 per cent) than in the group receiving carprofen (17 per cent) (P = 0.015) administered subcutaneously. A significant fall in water consumption occurred in the control group (40 per cent) and in animals that received oral carprofen (13 per cent) or Ketoprofen (22 per cent). No significant decrease was seen in groups receiving either carprofen or ketoprofen administered subcutaneously (P > 0.1). This study shows that a relatively simple surgical procedure results in a major reduction in food and water consumption in rats. This reduction can be minimised by the administration of ketoprofen or carprofen (5 mg/kg subcutaneously), but higher dose rates are required if these drugs are to be administered by the oral route.     

Metabolite concentrations in plasma following treatment of cattle with five anthelmintics

Plasma concentrations of anthelmintics and their metabolites were determined after cattle were treated at recommended dose rates and routes of administration. Fenbendazole, oxfendazole, febantel, albendazole and thiabendazole were given orally and oxfendazole was also administered with an intraruminal injector. After fenbendazole, oxfendazole and febantel were administered, fenbendazole, oxfendazole and fenbendazole sulphone were all detected in plasma in each case. However, there were marked differences between the three anthelmintics in the peak concentrations and areas under the plasma concentration/time curve (AUC) of these three metabolites. Intraruminal administration of oxfendazole produced higher AUC for fenbendazole and fenbendazole sulphone than did oral administration. Albendazole sulphoxide and sulphone were detected in cattle plasma after albendazole administration but no parent drug was present. These metabolites disappeared more rapidly in cattle than has been reported for sheep. Only 5(6)hydroxythiabendazole was detected in cattle plasma after thiabendazole treatment.