Target animal safety testing of an oral salicylanilide suspension, oxyclozanide, for the treatment of fascioliasis in bovine in China.

The aim of this study was to determine the potential toxicity risk of an oxyclozanide suspension to the target animal, bovine. In this experiment, 32 Simmental beef cattle were fattened and fed a full-price diet without antimicrobial agents. The test cattle were divided into 4 groups, which were treated with 0, 1, 3, and 5 times the recommended dosage through continuous intermittent oral administration at intervals of 2 days. The body weight of the cattle was recorded before and after the experiment, and the weight changes were calculated. The safety of the drugs was evaluated by weight gain, observation of clinical toxicity, haematology, clinical chemistry and histopathology. The results showed that the cattle had different degrees of diarrhoea, loss of appetite and depression after administration. The results of clinicopathology had no significant effect. The results of pathological examination showed that there was a certain degree of damage in the 5 times recommended dose group. The recommended dose was safe to use. Thus, the recommended dose should be given by a single oral administration to ensure the safe use of this drug in the clinic.

Antihelminthic potential of quinacrine and oxyclozanide against gill parasite Microcotyle sebastis in black rockfish Sebastes schlegeli.

The aim of this study was to assess the treatment potential of quinacrine and oxyclozanide against Microcotyle sebastis (Monogenea: Polyopisthocotylea) infection in cultured black rockfish Sebastes schlegeli. The oral administration of quinacrine led to a reduction in the mean abundance of M. sebastis infection in all quinacrine-treated groups, and the groups of fish administered quinacrine at 50, 100, and 200 mg kg(-1) for 3 consecutive days showed a parasite mean abundance that was 50 to 30% lower compared to that of the control group, suggesting that quinacrine has a therapeutic potential against M. sebastis. Although oxyclozanide showed a very high in vitro killing activity, in oral administration experiments, only the groups of fish administered 200 mg kg(-1) showed less than 50% mean abundance of M. sebastis compared to the control groups, suggesting that the absorption efficiency of orally administered oxyclozanide might be low in black rockfish and/or that M. sebastis might be less sensitive to orally ingested oxyclozanide. As praziquantel has been the sole therapeutic against M. sebastis infection in Korea for a long time, a broadening of available control measures is advisable in order to reduce the possible emergence of praziquantel-resistant M. sebastis. In our study, although quinacrine and oxyclozanide showed a therapeutic potential against M. sebastis, the treatment efficacy was not high enough to replace praziquantel. Thus, after investigations on the pathological effects and pharmacodynamics, use of quinacrine or oxyclozanide in combination with praziquantel may be considered as a way to prevent praziquantel resistance in M. sebastis.

Comparative pharmacokinetics of levamisole-oxyclozanide combination in sheep and goats following per os administration.

Since there is no registered anthelmintic drug available for use in goats, extra-label use of drugs is a common practice in most countries. The aim of the present study was to compare the pharmacokinetic disposition of levamisole (LVM)-oxyclozanide (OXZ) combination in sheep and goats following per os administration. Goats (n = 8) and sheep (n = 8) 12- to 16-months-old were used for this study. The animals received tablet formulation of LVM and OXZ combination orally at a dose of 7.5 mg/kg and 15 mg/kg body weight, respectively. Blood samples were collected by jugular vein at different times between 5 min and 120 h after drug administrations. The plasma concentrations of LVM and OXZ were analyzed by HPLC following liquid-liquid phase extraction procedures. The plasma concentrations and systemic availabilities of both LVM and OXZ in goats were lower and the plasma persistence of LVM was shorter compared with those observed in sheep. Terminal half-lives (t1/2λz) of both molecules are shorter in goats compared with those in sheep. Goats treated with LVM-OXZ combination at the recommended dose for sheep may result in a reduced efficacy, because of under-dosing, which may increase the risk of drug resistance in parasites. Increased or repeated dose could be a strategy to provide higher plasma concentration and thus to improve the efficacy against the target parasites in goats compared with sheep. However, some adverse reactions may occur since LVM has relatively very narrow therapeutic index due to its nicotine-like structure and effect.

Étant donné qu'il n'y a aucun anthelminthique homologué disponible pour utilisation chez les chèvres, l'utilisation hors-homologation de médicaments est une pratique usuelle dans la plupart des pays. L'objectif de la présente étude était de comparer la disposition pharmacocinétique de la combinaison levamisole (LVM)-oxyclozanide (OXZ) chez les moutons et les chèvres suite à l'administration per os. Des chèvres (n = 8) et des moutons (n = 8) âgés de 12 à 16 mois furent utilisés pour cette étude. Les animaux ont reçu une combinaison de comprimés de LVM et d'OXZ à une dose de 7,5 mg/kg et 15 mg/kg de poids corporel, respectivement. Des échantillons sanguins furent prélevés par ponction de la veine jugulaire à différents temps entre 5 min et 120 h suite à l'administration des médicaments. Les concentrations plasmatiques de LVM et d'OXZ furent analysées par HPLC suite à des procédures d'extraction de phase liquide-liquide. Les concentrations plasmatiques et les disponibilités systémiques de LVM et OXZ chez les chèvres étaient plus basses et la persistance plasmatique de LVM de plus courte durée comparativement à celles observées chez les moutons. Les demi-vies terminales (t1/2λz) des deux molécules sont plus courtes chez les chèvres comparativement à celles chez les moutons. Le traitement de chèvres avec la combinaison LVM-OXZ au dosage recommandé pour les moutons pourrait résulter en une efficacité moindre, dû à un sous-dosage, ce qui pourrait augmenter le risque de résistance au médicament chez les parasites. Des doses augmentées ou répétées pourraient s'avérer une stratégie pour obtenir des concentrations plasmatiques plus élevées et ainsi améliorer l'efficacité contre les parasites ciblés chez les chèvres comparativement aux moutons. Toutefois, quelques réactions indésirables peuvent survenir étant donné que le LVM a déjà un index thérapeutique assez étroit associé à sa structure et son effet apparentés à la nicotine.(Traduit par Docteur Serge Messier).

Point prevalence of bovine fascioliasis and the influence of chemotherapy on the milk yield in a lactating bovine population from the district of Toba Tek Singh, Pakistan.

This paper provides an estimation of the point prevalence of fascioliasis and its economic impact in terms of increased milk yield after chemotherapy of a bovine population from the district of Toba Tek Singh, Punjab, Pakistan. A total of 2400 cattle and buffaloes were examined quantitatively using the McMaster egg-counting technique. Infected cattle and buffaloes (50 of each) were randomly selected and each divided into two groups of 25 animals. Groups A (buffaloes) and C (cattle) were treated with oxyclozanide (orally, 16.6 mg kg- 1 body weight). Groups B and D served as negative controls for buffaloes and cattle, respectively. Pre- and post-treatment milk yield was recorded to determine if there were any changes in milk yield after treatment. Of 2400 faecal samples analysed, 654 (27.25%) were positive for Fasciola spp. with a mean number of eggs per gram (EPG) of 503.2. The point prevalence and worm burden of fascioliasis was significantly higher (OR = 2.13; P < 0.05) in buffaloes (34.58%; 415/1200; mean EPG maximum likelihood = 521.4) as compared to that of cattle (19.92%; 239/1200; mean EPG maximum likelihood = 415.8). Among the parasite species, F. gigantica (19.88%; 477/2400) was predominant (OR = 3.12; P < 0.05) as compared to F. hepatica (7.38%; 177/2400). An average daily increase of 0.67 and 0.87 litres of milk, with 0.41% and 0.37% more fat per animal, was observed in oxyclozanide-treated buffaloes and cattle, respectively. The economic value of reduced production of infected animals was estimated as US$0.33 and 0.32 per animal per day for cattle and buffaloes, respectively.

[The investigation of short term efficiency of oxfendazole + oxyclozanide paste and tablet formulations against gastrointestinal nematodes in sheep]. / Koyunlarda Mide-Bagirsak Nematodlarina Karsi Oxfendazole + Oxyclozanide'nin Tablet ve Pasta Formülasyonlarinin Kisa Süreli Etkinliginin Arastirilmasi.

The aim of this study was to investigate the effectiveness of tablet and paste formulations of Oxfendazole and Oxyclozanide combinations against subclinical gastrointestinal nematode infections and to compare the advantages and/or disadvantages of their use. Seventy-five infected sheep were selected from an enterprise located in Kayseri in 2006. The sheep were divided into 3 equal groups as paste, tablet and control groups. Fecal samples were collected from each group before drug administration. While the paste and tablet groups were administered drugs orally, no drugs were given to the controls. Fecal samples were collected on the 7th, 14th, 21st, and 28th days after drug application and the EPG values were determined. The parasitological examination revealed that the most prevalent species was Ostertagia spp., followed by Nematodirus spp. and Trichostrongylus spp. While the mean EPG value of the control group increased up to a ratio of 7.8% at day 28, the mean EPG values of drug groups decreased to 0%. Although the unit dose of paste formulation is more expensive, it was found that it could be an alternative to tablet formulation and has some advantages such as being easier to give, effective utilizing, shorter application period, fewer complications and death risk, no application failure and requires fewer personnel.

[Concentration in plasma and excretion in milk of lactating cows after oral administration of tribromsalan, oxyclozanide and bromofenofos].

The fasciolicides tribromsalan (TBS), oxyclozanide (OCZ) and bromofenofos (BFF) were orally administered to three lactating cows. The concentrations of TBS, OCZ and the BFF metabolite dephosphate bromofenofos (DBFF) in plasma, and the excretion of these compounds in milk were determined by high-performance liquid chromatography. In plasma, the concentrations of TBS, OCZ and DBFF reached maximum at about 1.0 day and the compounds remained detectable until 5.7, 7.4 and 15.1 days after administration, respectively. The detection limits of these compounds in plasma were 10, 2 and 2 ppb, respectively. In milk, the concentrations of TBS, OCZ and DBFF reached maximum at about 24 hours and the compounds remained detectable until 30-47, 30-47 and 78-119 hours after administration, respectively. The detection limits of these compounds in milk were 5.1 and 1 ppb, respectively. The residence times of TBS and BFF were very close to the withdrawal times of the fasciolicides.

The efficacy of triclabendazole and other anthelmintics against Fasciola hepatica in controlled studies in cattle.

In eight controlled tests 274 cattle were used to assess the efficacies of triclabendazole, albendazole, clorsulon, nitroxynil, oxyclozanide and rafoxanide against Fasciola hepatica. Against one-, two- and four-week-old early immature fluke the mean efficacies of triclabendazole given orally at 12 mg/kg were 88.1, 95.3 and 90.7 per cent, respectively. Clorsulon, nitroxynil and rafoxanide administered at recommended dose rates showed negligible activity against these stages of the parasite. Against six- and eight-week-old infections the mean efficacies of triclabendazole at 12 mg/kg were 87.5 per cent and 95.7 per cent, respectively. Against F hepatica aged six weeks, albendazole and oxyclozanide showed no activity and clorsulon, nitroxynil and rafoxanide had only slight to moderate activity. The efficacies of triclabendazole, clorsulon, nitroxynil and rafoxanide against 10- or 12-week-old parasites were 100, 99.0, 99.1 and 90.1 per cent, respectively. Albendazole and oxyclozanide showed poor efficacy against 12-week-old infections.

Control of selenium and cobalt deficiency in lambs by supplementation of oral anthelmintics.

The benefits of the inclusion of cobalt and selenium supplements in anthelmintic preparations were demonstrated in a 10 week trial with cobalt- and selenium-deficient blackface wethers. The anthelmintics were based on oxfendazole and on levamisole plus oxyclozanide; three doses provided, in total, 38 mg cobalt and 7.2 or 11.3 mg selenium. Administration of the supplements prevented the weight loss and reduction in food intake observed in unsupplemented animals. Blood glutathione peroxidase activities were restored to normal and increases in serum vitamin B12 levels were observed which were consistent with the prevention of both cobalt and selenium deficiencies.

Humoral and cellular response to infection with Echinostoma revolutum in the golden hamster, Mesocricetus auratus.

Laboratory hamsters (Mesocricetus auratus) were infected with Echinostoma revolutum (Trematoda). Immunoelectrophoretic studies of hamster serum showed no demonstrable antibody response to E. revolutum. Histopathologic examination of intestinal tissue of infected hamsters showed erosion of intestinal villi and lymphocytic infiltration as the primary host response. Spleens from infected hamsters were hyperplastic during the first 3 weeks of infection and atrophic from 4 to 8 weeks postinfection. Hamsters were unable to acquire a resistance to E. revolutum infection. Lack of resistance was demonstrated in hamsters where the parasite infection was no longer detected based on the absence of eggs in the faeces; these hamsters were then reinfected. Hamsters treated with the anthelmintic oxyclozanide were also reinfected with E. revolutum.

[Study of the therapeutic efficacy of Nilsan preparation against Paramphistomatidae and nematode infections in sheep]. / Prouchvane vurkhu terapevtichniia efekt na preparata Nilsan sreshchu paramfistomatozata i nematodozite po ovtsete.

Experiments were carried out with the preparation Nilsan (oxiclozanide + levamizal) in the treatment of sheep with Fasciola, Dictyocaulus, and Trichostrongylus infection. The trials involved a total of 2782 sheep on two sheep-breeding farms, constituting 15 flocks. The liveweight of the adult animals ranged from 40 to 60 kg, and that of the year-old female ones--from 40 to 45 kg. The daily ration on the two farms did not differ essentially from that offered to the animals in the past 2-3 years. It was found that at the rate of 22 to 28 cm3 per head Nilsan produced 76.67 to 96.67 percent effect against Paramphistomum infection, 100 percent effect against Dictyocaulus infection, 73.37 to 90.00 percent effect against Trichostrongylus infection, and 23.34 to 83.34 percent effect against Dicrocelium infection. The application of an ex tempore combination of oxiclozanide and levamizal to sheep at the rate of 24 cm3 per head produced 86.67 to 100 percent effect against Paramphistomum, 96.67 to 100 percent effect against Dictyocaulus, 86.67 to 96.67 percent effect against Trichostrongylus, and 46.67 to 86.67 percent effect against Dicrocelium. The experimental sheep produced 16.41 to 37.40 per cent more wool, 0.85 to 35.09 per cent more milk, and 8 to 12 per cent more weight gain.

[Effectiveness of levamisole and oxyclozanide in paramphistomiasis in sheep and cattle]. / Efektivnost na levamizole i oxyclozanide sreshtu paramfistomatozata po ovtsete i govedata.

The antiparasitic effectiveness of Levamizole and Oxyclozamide in the control of paramphistomatosis in sheep and cattle was studied. Experiments were performed in the 1975--1978 period with 1880 sheep and 132 cattle naturally invaded by P. microbothrium. The two drugs were administered orally in the following doses: Levamizole -- 7.5 mg/kg, Oxyclozanide -- 15 mg/kg for sheep and 10 mg/kg for cattle. A part of the experimental animals were treated by the combined drug Nilzan and received the above mentioned doses of both chemico-therapeutic means. Results were scored by ovoscopic investigation on the 10th and 15th day post treatment and by helminthological investigation on a part of the animals. Egg deposition was followed on 1415 sheep in the course of 4 months. A comparatively low effectiveness of Levamizole was established, namely U = 15--50%, IU = 81.56--99.40% and a good effectiveness of Oxyclozanide application, namely -- U = 30--80%, IU = 73.94-- 99.40% for sheep, and U = 0--50%, IU = 74.84--89.97% for cattle. Highest effectiveness was observed following the application of the combined drug Nilzan -- U = 47.7--92.0%, IU = 89.07--99.98% for sheep, and U = 20--73.20%, IU = 99.32--99.96% for cattle. The enhanced effectiveness of Nilzan application is considered by the authors as a result of synergism of the two chemico-therapeutic means.

[Effectiveness of oxyclozanide in cattle naturally invaded by Liorchis scotiae trematoda]. / Ucinnost preparátu oxyklozanid u dobytka pribodzene invadovaného trematodmi Liorchis scotiae

The paper reports on the results of the clinical tests for the effectiveness of oxyclozanide pure substance (produced by ICI, U.K.) in cattle naturally invaded by the paramphistomata Liorchis scotiae. Helminthological dissection, performed 21 days after a single application of 15 mg oxyclozanide per 1 kg 1. w., revealed 87.5% intenseffectiveness on sexually mature paramphistomata on 85% intenseffectiveness on juvenile paramphistomata. The extenseffectiveness of the chemical was equal to zero. The coprological examinations performed for the three weeks in one-week intervals after therapy showed a decline in the number of produced eggs. The animals were given the medicated feed containing oxyclozanide only after preceding starvation. The chemical did not produce any unfavourable side effects or signs.