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 use of cultured hepatocytes from goats and cattle to investigate xenobiotic oxidative metabolism

The oxidative metabolism of aldicarb (ALD), a carbamate pesticide, and fenbendazole (FBZ), an anthelmintic, was studied using cultured hepatocytes obtained from 4 goats and a bullock and incubated with ALD (50 mol/L) and FBZ (10 mol/L). The parent compounds and the metabolites were measured by HPLC. Both compounds are metabolized at the sulphur atom via two sequential oxidations, first to the sulphoxide (aldicarb sulphoxide and oxfendazole, respectively) and then to the sulphone. Oxfendazole and fenbendazole sulphone from FBZ, and aldicarb sulphoxide from ALD were found in both species. Aldicarb sulphone was not produced by the hepatocyte preparations from the bullock. The good correlation obtained comparing the in vitro results of FBZ metabolism with published in vivo dat obtained on FBZ kinetics in the same species confirmed the usefulness of in vitro models for predictive analysis of in vivo xenobiotic biotransformations.Abbreviations ALD aldicarb - ALDSON aldicarb sulphone - ALDSOX aldicarb sulphoxide - BSA bovine serum albumin - ID internal diameter - EGTA ethylene glycol bis(-aminoethyl ether) N,N,N,N-tetraacetic acid - FBZ fenbendazole - FBZSON fenbendazole sulphone - HBSS Hanks' balanced saline solution - HPLC high-pressure liquid chromatography - LDH lactate dehydrogenase - MFO mixed function oxidase - NCS newborn calf serum - OXF oxfendazole - WME Williams' Medium E     

Efficacy of bath and orally administered praziquantel and fenbendazole against Lepidotrema bidyana Murray,a monogenean parasite of silver perch,Bidyanus bidyanus (Mitchell)

We investigated the efficacy of praziquantel (PZQ) and fenbendazole (FBZ), each administered by bath and orally, against the monogenean Lepidotrema bidyana Murray, a gill parasite of the freshwater fish silver perch, Bidyanus bidyanus (Mitchell). PZQ and FBZ were each administered by bath at 10 mg L^?1 for 48 h and on surface‐coated feed pellets at 75 mg kg^?1 per body weight (BW) per day for 6 days. Bath treatments of PZQ and FBZ had an efficacy of 99% and 91%, respectively, against adult L. bidyana. Oral treatments of PZQ and FBZ had an efficacy of 79% and 95%, respectively, against adult L. bidyana. Fish rejected feed pellets surface‐coated with PZQ, suggesting that palatability of surface‐coated PZQ‐medicated feed is poor, which undermined efficacy. In all trials, some juvenile parasites were present on fish after treatment during efficacy assessment, indicating that efficacy may be lower against juvenile parasites or that recruitment occurred post‐treatment, demonstrating that repeat treatments are necessary to effectively control L. bidyana in aquaculture.     

对2005年版中国兽药典芬苯达唑鉴别方法的商榷

对2005年版《中国兽药典》芬苯达唑鉴别方法中紫外-可见分光光度法测定最大吸收波长存在的问题进行了讨论。建议采用色谱纯甲醇及选择296 nm波长处最大吸收进行芬苯达唑鉴别(1)的测定。     

Efficacy of single and multiple doses of fenbendazole against gill parasites (Dactylogyrus sp.) of Labeo rohita (Hamilton, 1822) and its physio‐metabolic effects on the fish

The study was conducted to investigate the efficacy and physio‐metabolic responses of single and multiple doses of fenbendazole (FBZ) in Labeo rohita against gill parasite (Dacylogyrus sp.). Two Isoenergetic (395 Kcal DE/100 g) and isonitrogenous (35% CP) purified diets viz. control (without FBZ) and treatment (0.2% FBZ) were prepared. The efficacy of FBZ was measured after administration of single dose (20 mg/kg b. wt.) on 0th day and multiple doses of FBZ, that is, 20 mg/kg b. wt. on 0th, 3rd and 7th day through diet. Although oral administration of FBZ at single dose could significantly reduce the parasite in fish in comparison with the control group, 100% efficacy of the drug was not achieved up to 15th day of treatment. On the other hand, multiple doses of FBZ could show almost 100% efficacy on 15th day in terms of elimination of parasites from gill. The drug induced oxidative stress in examined fish. There was no significant change in activities of hepatic and muscle aspartate aminotransferase and alanine aminotransferase of L. rohita up to 15th day after oral administration of FBZ at single dose. But both single and multiple doses of FBZ could significantly enhance the hepatic superoxide dismutase, catalase and glutathione‐S‐transferase activities in fish up to 7th day of drug administration and significantly decreased thereafter up to 15th and/or 30th day. It is concluded that oral administration of FBZ at multiple doses (20 mg/kg b. wt.) on 1st, 3rd and 7th day could be effective against Dactylogyrus sp. infection in L. rohita.     

The effect of peri-parturient anthelmintic treatment on the productivity of dairy cattle in subtropical western India

Trials with fenbendazole (Panacur, Hoechst India Ltd) were carried out on two commercial farms in subtropical western India to study the response and economics of nematode treatment in adult dairy cows. Milk yield, lactation length, time to first oestrus and worm egg output were monitored in treated and control groups. Treatment reduced the egg count considerably. Treated cows produced 142 litres more milk over 100 days (p<0.05), with extension of lactation length and advancement of time to first oestrus. The economic gain in terms of milk yield far outweighed the cost of anthelmintic used.     

Assessment of the pharmacological interactions between the nematodicidal fenbendazole and the flukicidal triclabendazole: In vitro studies with bovine liver microsomes and slices

Parasitic diseases have a significant impact on livestock production. Nematodicidal drugs, such as fenbendazole (FBZ) or its oxidized metabolite oxfendazole (OFZ), can be used along with the trematodicidal triclabendazole (TCBZ), to broaden the spectrum of anthelmintic activity. However, co‐exposure to these compounds could lead to drug–drug (D‐D) interactions and eventually alter the clinical profile of each active principle. The aim of this study was to assess the presence of such interactions by means of two in vitro models, namely bovine liver microsomal fractions and bovine precision‐cut liver slices (PCLSs). To this end, an in vitro assessment involving incubation of FBZ and TCBZ or a combination of FBZ and TCBZ was carried out. Results with microsomal fractions showed a 78.4% reduction (p = .002) in the rate of OFZ production upon co‐incubation, whereas the sulfoxide metabolite of TCBZ (TCBZSO) exhibited a decreasing tendency. With PCLS, OFZ accumulation in the incubation medium increased 1.8‐fold upon co‐incubation, whereas TCBZSO accumulation decreased by 28%. The accumulation of FBZ and OFZ in the liver tissue increased upon 2‐hr co‐incubation, from 2.1 ± 1.5 to 18.2 ± 6.1 (p = .0009) and from 0.4 ± 0.1 to 1.3 ± 0.3 nmol (p = .0005), respectively. These results confirm the presence of D‐D interactions between FBZ and TCBZ. Further studies are needed to determine the extent of involvement of drug‐metabolizing enzymes and membrane transporters in interactions between compounds largely used in livestock production systems.     

Pharmacokinetics and metabolism of fenbendazole in channel catfish

Fenbendazole (FBZ) was administered intravenously (1 mg/kg) and orally (5 mg/kg) to catheterized, confined channel catfish. Blood samples were collected for 72 h, and resulting FBZ plasma concentrations were pharmacokinetically modelled. Following intravenous administration t1/2 was 0.51 h, t1/2 was 16.8 h, body clearance (C1b) was 0.0598 L/kg/h, and Vd (area) was 1.45 L/kg. After oral administration the t1/2 (abs) was 1.47 h, the t1/2 was 20.1 h, and the tlag was 0.1 h.Following oral administration of 5 mg FBZ/kg body weight, the following tissues and body fluids were sampled for concentrations of FBZ, oxfendazole (FBZ-SO), sulphone metabolite (FBZ-SO₂) and hydroxy metabolite (FBZ-OH): liver, posterior kidney, fat, muscle, bowel contents and urine. Fenbendazole was detected in the highest concentrations in abdominal fat, whereas oxfendazole was found primarily in the kidney, liver and abdominal fat. The sulphone metabolite was detected only in urine and bowel contents, while the hydroxy metabolite was found most often in the liver and abdominal fat samples.