奥芬达唑和阿苯达唑对猪囊尾蚴作用形态学比较观察

观察了奥芬达唑和阿苯达唑对猪体内及体外培养的不同发育阶段囊尾蚴作用的形态学效果.结果表明奥芬达唑具有显著的疗效,优于阿苯达唑,且对未成熟期猪囊尾蚴的杀灭作用优于成熟期.提示奥芬达唑可能成为抗未成熟期猪囊尾蚴及治疗脑囊虫病的有效药物.     

Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows

Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO₂) into milk. The goal of this study was to evaluate the presence of potential in vivo drug‐drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO₂ was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO₂ into milk was observed. The milk‐to‐plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO₂ were not modified in the presence of OFZ. The pattern of MNPSO₂ excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO₂) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO₂) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the in vivo pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO₂.     

阿苯达唑和奥芬达唑对体外培养猪囊尾蚴能量代谢变化的影响

测定了在阿苯达唑和奥芬达唑作用下体外培养猪囊尾蚴磷酸烯醇式丙酮酸羧激酶（PEPCK）、丙酮酸激酶（PK）、延胡索酸还原酶（FR）、苹果酸酶（ME）活性的变化及葡萄糖（GLC）、乳酸（LAC）含量的变化。结果表明，2种药物作用均可在体外作用条件下显著改变未成熟期及成熟期猪囊尾蚴的能量代谢。提示，苯并咪唑氨基甲酸酯类药物的作用机理可能是通过干扰虫体能量代谢，阻断能量的产生，导致虫体死亡。     

Some Pharmacokinetic Parameters of Oxfendazole in Sheep

Soraci, A.L., Mestorino, N. and Errecalde, J.O., 1997. Some pharmacokinetic parameters of oxfendazole in sheep. Veterinary Research Communications, 21 (4), 283-287     

Naphthalophos combinations with benzimidazoles or levamisole as effective anthelmintics for sheep

Objective: To investigate the relative efficacy and safety of the anthelmintic naphthalophos in sheep, either given alone or in combination with benzimidazole (fenbendazole and albendazole) or levamisole anthelmintics.
Design: A parasitological study using faecal egg count reduction tests, a validating slaughter trial and field safety trials.
Procedure: Faecal egg count reduction tests were carried out on 13 farms. Naphthalophos and combinations of naphthalophos with levamisole and fenbendazole were included in the drench tests. On one property a controlled efficacy study was carried out to validate faecal egg count reduction test findings. In this trial, sheep were slaughtered 10 days after treatment and the remaining parasites recovered from the gastro-intestinal tract. Safety trials were carried out on eight farms where approximately 50 000 sheep were treated with naphthalophos and albendazole that were tank mixed in the backpack.
Results: The efficacy of naphthalophos alone in faecal egg count reduction tests ranged from 59 to 98% with one test showing 95% reduction. The efficacy of naphthalophos and levamisole ranged from 74 to 100%, with 5 farms showing 95% reduction. The efficacy of naphthalophos and fenbendazole ranged between 88 and 100% with 95% reduction achieved on 10 farms. The controlled efficacy study showed a good correlation between the faecal egg count reduction tests and numbers of parasites recovered, except for Nematodirus where the faecal egg count reduction tests overestimated efficacy. The mortality rate in the safety trials was 0.05%, with most fatalities occurring on one farm.
Conclusion: The combination of naphthalophos and fenbendazole was more effective than a combination of naphthalophos and levamisole, and will provide a sufficiently safe drench rotation option.     

The Target of Benzimidazole Carbamate Against Cysticerci cellulosae

To study the target of benzimidazole carbamate drugs against Cysticerci cellulosae and give a theoretical basis for type evolution and new drug design, the changes of key enzyme activities and metabolite contents in the pathway of energy metabolism in C. cellulosae in vitro and in vivo were tested with albendazole and oxfendazole, respectively. Both albendazole and oxfendazole inhibited the pathways of anaerobic glycolysis, partial inversed tricarboxylic acid cycle of Taenia Solium oncosphere, immature and mature Cysticerci in vitro, and immature and mature Cysticerci in vivo to a certain degree, and enhanced fat decomposing, amino acid decomposing, xanthine decomposing metabolism, and on the other hand, the absorption of glucose was hindered; furthermore, both albendazole and oxfendazole inhibited the activities of the fumaric reductase （FR） complex noncompetently in vitro. Benzimidazole carbamate drugs could inhibit the activities of FR complex noncompetently and hinder the absorption of glucose.     

Inhibition of Albendazole and Oxfendazole on the Activity of Fumaric Reductase in Cysticercus cellulosae

The activity of fumaric reductase in Cysticercus cellulosae tissue homogenate with albendazole and oxfendazole individually was detected. Results showed that the two kinds of drugs both could inhabite the activity of fumaric reductase. The results indicate that the mechanism of action of benzimidazole carbamate drugs is probably inhabiting the complex of fumaric reductase noncompetently, thus lead to the exhaostion of energy and death.     

The uptake of fenbendazole by cattle and buffalo following long-term low-level administration in urea-molasses blocks

Fenbendazole (Panacur bolus, Hoechst India Ltd) was incorporated at a rate of 0.5 g/kg into urea-molasses blocks made by two different processes. The concentration of the drug in blocks and its bioavailability were measured using plasma oxfendazole as marker. The recovery of the drug in blocks made by a warm process was 68% and the plasma oxfendazole concentration remained fairly stable at 0.2 and 0.12 µg/ml from day 6 of feeding in cattle and buffalo, respectively. The drug seemed to be inactivated in blocks made by a hot process, with reduced bioavailability. A low and sustained plasma concentration of the active metabolite of the drug could be maintained by self-medication using urea-molasses blocks as fenbendazole carrier.Abbreviations FBZ fenbendazole - HPLC high-performance liquid chromatography - MUMB medicated urea-molasses blocks - OFZ oxfendazole - UMB urea-molasses block     

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.     

A survey of the prevalence of emerging macrocyclic lactone resistance and of benzimidazole resistance in sheep nematodes in the lower North Island of New Zealand

AIM: To investigate the occurrence of emerging macrocyclic lactone (ML) resistance and of resistance to benzimidazole anthelmintics on a number of sheep farms in the North Island of New Zealand.

METHODS: On commercial sheep farms (n=30) in the Taihape district in the North Island of New Zealand, 30 animals were randomly allocated to one of two equal-sized groups and treated with either half of the recommended dose rate of ivermectin (half of 0.2 mg/kg), or with the full recommended dose rate of oxfendazole (4.5 mg/kg). The ivermectin treatment only was used on a further six properties. Faecal egg counts, accompanied by pooled larval cultures, were conducted on all samples at the time of treatment and 7–10 days later.

RESULTS: Resistance, as indicated by a <95% faecal egg count reduction (FECR) in both instances, was found to oxfendazole on 13/30 (43%) farms and to a half dose of ivermectin on 12/36 (33%) properties. For oxfendazole, such resistance was found to involve all six nematode genera whereas for ivermectin it was almost entirely restricted to Ostertagia and Cooperia infections.

CONCLUSIONS: These results indicate that emerging ML resistance may be more common on sheep farms in New Zealand than is generally realised. They also suggest that the half-dose ivermectin faecal egg count reduction test (FECRT) may offer some very practical benefits for parasite control by providing early warning of developing resistance to ML drenches and by signalling the possible imminent failure of these at their therapeutic dose rates. The sensitivity and reliability of this procedure may be further enhanced by the inclusion of larval cultures.