Enhanced Plasma Availability of the Metabolites of Albendazole in Fasted Adult Sheep

Lifschitz, A., Virkel G., Mastromarino, M. and Lanusse C., 1997. Enhanced plasma availability of the metabolites of albendazole in fasted adult sheep. Veterinary Research Communications, 21 (3), 201-211The influence of fasting prior to treatment and of dosing rate on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites was studied in adult sheep grazing on pasture. A micronized suspension of ABZ was administered orally at either 7.5 mg/kg (group A) or 11.3 mg/kg (group C) to sheep fed ad libitum, and at 7.5 mg/kg to sheep subjected to a 24 h fasting period prior to treatment (group B). Blood samples were taken serially over 96 h after treatment, and the plasma was analysed for ABZ and its metabolites by high-performance liquid chromatography. ABZSO and ABZSO2 were recovered from the plasma. Fasting induced marked modifications in the pharmacokinetic behaviour of the ABZ metabolites in sheep. An extended absorption process, with a delayed peak concentration in the plasma, was observed for both metabolites in the fasted sheep. Significantly higher area under the curve (AUC) and peak plasma concentration (Cmax) values were obtained for both metabolites in the fasted animals compared to those fed ad libitum. Delayed elimination with prolonged detection in plasma was also observed in the fasted sheep. Treatment with ABZ at 7.5 mg/kg in the starved animals resulted in bioequivalence to the administration of the compound at a 50% higher dose rate (11.3 mg/kg) in the fed animals. It is suggested that fasting enhances ABZ dissolution and absorption by delaying its passage down the digestive tract.     

宁夏羊胃肠道线虫对现行驱虫药的抗药性调查

采用粪便虫卵减少试验对宁夏地区所属灵武、贺兰、盐池、吴忠、中宁、中卫、永宁和银川市郊8个县（市）的12个绵羊场、6个山羊场进行了丙硫苯咪唑和阿维菌素抗药性的随机调查。结果表明：在用丙硫苯咪唑调查的10个绵羊场和6个山羊场中，虫卵减少率在95％以下和95％的置信域下限在90％以下的有山羊场2个、绵羊场2个，证明对丙硫苯咪唑有抗药性；1个绵羊场和1个山羊场的虫卵减少率是96．3％、95．9％，但95％置信域的下限在90％以下，具有抗药性可疑；山羊群中丙硫苯咪唑的抗药性为33．3％，绵羊群为20．0％。用同样的方法调查了1个山羊场和5个绵羊场（其中有4个羊场曾执行了丙硫苯咪唑的试验），查出1个山羊场和1个绵羊场对阿维菌素具有抗药性可疑，其虫卵减少率分别为97．3％和95．5％，置信域下限在90％以下。揭示了宁夏地区羊消化道线虫对现行驱虫药的抗药状态，为今后防治提供了依据。     

牛羊线虫抗药性及其PC检测技术研究进展

牛羊线虫病是严重影响牛羊生产性能和经济效益的主要寄生虫病，化学药物是目前防治本病的主要手段，近年来线虫抗药性。已经成为世界各地牛羊线虫控制中的首要问题。建立线虫抗药早期检测技术可以时了解抗药性及其产生的条件等，便于采取有效对策，本文简要阐述牛羊线虫抗药性的分布与检测，现有抗药性检测方法的缺点以及PCR检测技术的最新进展。     

Effects of Diet and Species on the Pharmacokinetics of Fenbendazole in Cattle

Knox, M.R. and Steel, J.W., 1997. Effects of diet and species on the pharmacokinetics of fenbendazole in cattle. Veterinary Research Communications, 21 (1), 37-43.The plasma concentration profiles of fenbendazole (FBZ), FBZ-sulphoxide (OFZ) and FBZ-sulphone were measured following intraruminal administration of FBZ at 7.5 mg/kg bodyweight in Bos taurus and B. indicus cattle offered three different diets: 100% wheaten chaff, 100% lucerne, and a 50:50 mix of these two diets. No differences between the species were apparent except for a longer time to peak plasma concentration for OFZ in the B. taurus steers fed 100% wheaten chaff. Cattle fed wheaten chaff alone gave greater areas under the concentration-time curve and longer persistence for all metabolites than when the same cattle were fed the other diets. It is concluded that the reduced rate of passage of digesta on lower-quality fibrous diets allows greater time for absorption of FBZ and its metabolites from the gut, thereby increasing systemic availability.     

Resistance to benzimidazole anthelmintics in small strongyles (Cyathostominae) of horses in Denmark.

This study was undertaken to establish whether anthelmintic resistance was present in nematode parasites of horses in Denmark. Sixteen horse farms were selected for faecal egg count reduction (FECR) tests to measure the efficacy of the anthelmintic used. Resistance to benzimidazole anthelmintics was found on 13 of the 16 farms, with FECR values ranging from 80.0% to -101.3%. On the remaining 3 farms FECR was 100.0%, 99.3% and 97.2%. Results of a questionnaire study on anthelmintic usage, parasite control measures and management practices showed that horses in this study were treated on average 7.1 times/year. Horse owners changed between preparations of drugs but almost only within the same class of anthelmintics. Nine owners gave an anthelmintic treatment to purchased horses before they were introduced on the farm. On 14 farms, the same paddock was grazed every year and the average stocking rate was estimated to be 2.4 horses/ha. Strategies to avoid development of anthelmintic resistance are discussed and recommendations of parasite control on horse farms are presented.     

Minimising the development of anthelmintic resistance, and optimising the use of the novel anthelmintic monepantel, for the sustainable control of nematode parasites in Australian sheep grazing systems

Objective To compare the risk of different treatment scenarios on selecting for anthelmintic resistance on Australian sheep farms. Design A computer simulation model predicted populations of Trichostrongylus colubriformis, Haemonchus contortus or Teladorsagia (Ostertagia) circumcincta, and the frequency of anthelmintic resistance genes. Method Nematode populations and the progression of drug resistance for a variety of treatment options and management practices in sheep‐rearing areas of Western Australia (WA), Victoria (VIC) and New South Wales (NSW) were simulated. A scoring system was devised to measure the success of each option in delaying resistance to each anthelmintic and in controlling nematode populations. Results The best option at all sites was combining the new anthelmintic (monepantel) with a triple mixture of benzimidazole, levamisole and abamectin (COM). The next best option was: in NSW, rotation at each treatment between monepantel, moxidectin and COM; in VIC, rotation at each treatment between monepantel and COM; and in WA, rotation at each treatment between monepantel (used in winter) and COM or moxidectin (used in summer–autumn). In WA, rapid selection for resistance occurred as a consequence of summer–autumn treatments; however, if a small percentage of adult stock were left untreated then this selection could be greatly reduced. Despite purposely assuming relatively high resistance to benzimidazole and levamisole, COM was still effective in controlling worms and delaying resistance. Conclusions Because of cost constraints, it may not be feasible or profitable for producers to always use the combination of all drugs. However, the second‐ and third‐best options still considerably slowed the development of anthelmintic resistance.     

Fatal levamisole toxicosis of captive kiwi (Apteryx mantelli)

CASE HISTORY: Nine of 24 captive kiwi treated with oral levamisole at a dose between 25–43 mg/kg showed signs of respiratory distress. Six died within 4 h of treatment and the remaining three made a full recovery within 24 h.

CLINICAL AND PATHOLOGICAL FINDINGS: Within 3–4 h of treatment, the affected birds had an elevated respiratory rate, mucoid nasal discharge and rapidly became comatose. Post mortem examination revealed accumulation of thick mucus in the oral cavity and trachea. There was severe pulmonary congestion and oedema and early bronchopneumonia in the lungs of five of the birds. In two birds, there was acute hepatic degeneration and necrosis and one bird had acute pancreatic degeneration and necrosis.

DIAGNOSIS: Acute levamisole toxicity.

CLINICAL RELEVANCE: Kiwi were acutely sensitive to levamisole toxicity at doses that are well within the safe range for domestic poultry. Levamisole should not be used as an anthelmintic in kiwi.     

The Effect of Treatment with a 1% Injectable Formulation of Moxidectin during the Rainy Season and at the Beginning of the Dry Season on Gastrointestinal Nematodes in Cattle from Communal Areas in Zimbabwe

The effect of 1% moxidectin/cydectin at 0.2 mg/kg live weight on gastrointestinal nematodes and on the growth of calves, weaners and cows was investigated in five communal areas on the highveld of Zimbabwe. Three field experiments were carried out between March 1996 and June 1997. In experiment 1, treatment was administered in all five areas at the end of the rainy season in March 1996, followed by a further treatment at the beginning of the dry season in May/June 1996. In experiment 2, the treatment was administered in three areas at the end of the rainy season in March 1997. In experiment 3, treatment was administered in one area at the beginning of the dry season in April 1997. Large numbers of eggs were present in the faeces of calves and weaners at the start of experiments 1 and 2. Epg values were lower in cows and in all age categories in experiment 3. There was a statistically significant reduction in epg values in calves, weaners and cows following treatment with a reduction of 90–99% in all cases except in cows in experiment 3, where no meaningful assessment was possible owing to the low egg counts in both the treated and control cows. The dominating larval types in faecal cultures were Cooperia and Haemonchus. Trichostrongylus, Oesophagostomum and Bunostomum were also found. Following treatment, Haemonchus was suppressed far more than Cooperia. This may be related to a longer residual effect against abomasal parasites like Haemonchus in comparison to small intestinal worms like Cooperia. Anthelmintic treatment conferred significant weight gain advantages (p<0.05) on treated calves, weaners and cows. The weight gains are discussed in relation to disease and nutrition.     

Anthelmintic Activity of Extracts of Spondias mombin Against Gastrointestinal Nematodes of Sheep: Studies In Vitro and In Vivo

This study was carried out to validate the efficacy of Spondias mombin, used locally as an anthelmintic, and to standardize the effective dose of the plant extract required for worm control in livestock. In vitro and in vivo studies were conducted to determine the direct anthelmintic effect of ethanolic and aqueous extracts of S. mombin towards different ovine gastrointestinal nematodes. A larval development assay (LDA) was used to investigate the in vitro effect of extracts on strongyle larvae. Another study was conducted in vivo to evaluate the therapeutic efficacy of the extracts administered orally at dose rates of 125, 250, 500 mg/kg to sheep naturally infected with gastrointestinal nematodes. Twenty sheep were selected on the basis of positive faecal egg counts (750 epg). The sheep were allocated randomly to a non-medicated control group (A) or to groups given 125 mg/kg (B), 250 mg/kg (C) or 500 mg/kg (D) of extract, respectively. Sheep in groups B-D were given extracts orally on two days. Individual faecal egg counts were performed on days 0, 3, 6, 9 and 12. The presence of S. mombin extracts in in vitro cultures of larvae decreased the survival of L3 larvae. The LC50 of the aqueous extract of S. mombin was 0.907 mg/ml, while the LC50 of the ethanolic extract was 0.456 mg/ml. This difference in LC50 was statistically significant (p > 0.05). The mean percentage faecal egg reduction of sheep drenched with 500 mg/kg S. mombin extracts was 15.0%, 27.5%, 65.0%, 65.0%, 100.0% against Haenmonchus spp., Trichostrongylus spp., Oesophagostomunm spp., Strongyloides spp. and Trichuris spp. respectively, on day 12. Extracts of S. mombin could find application in the control of helminths in livestock.     

A Preliminary Study on the Anthelmintic Activity of Calotropis procera Latex against Haemonchus contortus Infection in Najdi Sheep

The anthelmintic activity of Calotropis procera latex was investigated in sheep that had been infected with single oral doses of 12 000 infective Haemonchus contortus larvae. Inappetence, dullness, erosive abomasitis, decreased haemoglobin concentration and increased eosinophils were the main features of haemonchosis in the sheep. In the sheep treated with single oral doses of 0.01 ml or 0.02 ml/kg body weight of C. procera latex, egg production was significantly reduced, but not completely suppressed, and fewer adult Haemonchus worms were found in the abomasum. Although the appetite improved, the haemoglobin concentration and serum copper, iron and zinc levels were still reduced after therapy with Calotropis latex. Calotropis latex showed a concentration-dependent larvicidal activity in vitro within 20 min of application.