febantel and oxfendazole

Topics: Albendazole; Animals; Anthelmintics; Benzimidazoles; Feces; Guanidines; Male; Monieziasis; Praziquantel; Sheep; Sheep Diseases

A liquid chromatography-electrospray-mass spectrometry method (LC/MS) has been developed and validated for determination of praziquantel (PZQ), pyrantel (PYR), febantel (FBT), and the active metabolites fenbendazole (FEN) and oxfendazole (OXF), in dog plasma, using mebendazole as internal standard (IS). The method consists of solid-phase extractions on Strata-X polymeric cartridges. Chromatographic separation was carried out on a Phenomenex Gemini C6 -Phenyl column using binary gradient elution containing methanol and 50 mm ammonium-formate (pH 3). The method was linear (r(2)  ≥ 0.990) over concentration ranges of 3-250 ng/mL for PYR andFEB, 5-250 ng/mL for OXF and FEN, and 24-1000 ng/mL for PZQ. The mean precisions were 1.3-10.6% (within-run) and 2.5-9.1% (between-run), and mean accuracies were 90.7-109.4% (within-run) and 91.6-108.2% (between-run). The relative standard deviations (RSD) were <9.1%. The mean recoveries of five targeted compounds from dog plasma ranged from 77 to 94%.The new LC/MS method described herein was fully validated and successfully applied to the bioequivalence studies of different anthelmintic formulations such as tablets containing PZQ, PYR embonate and FBT in dogs after oral administration.

Topics: Animals; Benzimidazoles; Chromatography, Liquid; Dogs; Female; Fenbendazole; Guanidines; Limit of Detection; Linear Models; Male; Mass Spectrometry; Praziquantel; Pyrantel Pamoate; Reproducibility of Results; Solid Phase Extraction; Therapeutic Equivalency

In this study, febantel was dissolved under increased temperature in a nonionic surfactant Lutrol L44® and subsequently mixed into an aqueous maltodextrin solution. After 8h under static conditions, coacervation or phase separation took place. (1)H NMR spectra and HPLC analysis showed that the upper phase contained mainly all febantel, while no febantel was detected in the lower phase. Fluorescent microscopy showed that maltodextrin is distributed in the lower phase. Coacervation proved to be a promising formulation technology for certain poorly water-soluble drugs, such as febantel. The coacervate phase showed an increase in in vitro dissolution kinetics, compared to Rintal® granules. These results were confirmed in an in vivo study performed on dogs. Febantel and fenbendazole showed a significant increase in plasma concentration compared to Rintal® granules. Further studies have to be performed to transform coacervates into a solid dosage form and to prove broad applicability to other poorly soluble drugs.

Topics: Animals; Area Under Curve; Benzimidazoles; Biopharmaceutics; Chemistry, Pharmaceutical; Dogs; Drug Design; Fenbendazole; Guanidines; Kinetics; Magnetic Resonance Spectroscopy; Microscopy, Fluorescence; Molecular Structure; Pilot Projects; Polyethylene Glycols; Solubility; Surface-Active Agents; Temperature; Water

In the present study the bioavailability of febantel paste and febantel suspension was investigated in the fully hydrated and the dehydrated camel. The serum concentrations of febantel and its metabolites, fenbendazole, oxfendazole and fenbendazole sulfone were determined by high performance liquid chromatography following extraction with ether. The exposure to febantel and its metabolites in fully hydrated camels was significantly higher in camels dosed with febantel paste compared to febantel suspension, as measured by AUC and Cmax. The AUC and Cmax of fenbendazole and oxfendazole were significantly lower in dehydrated camels as compared to control camels dosed with febantel paste. The systemic availability of febantel suspension in control and dehydrated camels was very low and differences between dehydration and control phases were insignificant. The low systemic availability of febantel in camels dosed with febantel suspension may cause nematodes to become resistant to this anthelmintic. It is, thus, suggested to increase the dose of febantel paste in dehydrated camels in order to increase the exposure to febantel and its metabolites. The binding of febantel, fenbendazole, oxfendazole and fenbendazole sulfone to camels' serum proteins was over 85%. Oxfendazole was only about 70% bound. Dehydration of 10 days did not affect the binding of these benzimidazole derivatives to serum proteins.

Topics: Administration, Oral; Animals; Anthelmintics; Benzimidazoles; Biological Availability; Camelus; Chromatography, High Pressure Liquid; Dehydration; Female; Fenbendazole; Guanidines

Liver tumor-promoting effects of anthelminthic agents, febantel (Feb), fenbendazole (Fen) or oxfendazole (Oxf), were investigated in a rodent 2-stage carcinogenesis model. Five-week-old male F344 rats were initiated with or without diethylnitrosamine (DEN) and one week later given diet containing Fen (3600, 1800, 600, 200 or 70 ppm), Feb (2000, 1000, 500 or 100 ppm) or Oxf (500, 250, 100 or 10 ppm) for 8 weeks. Induction of CYP1A1/2 was observed in treated groups of DEN + Feb and DEN + Oxf groups, and its induction was most marked in DEN + Oxf groups. CYP2B1 and CYP4AI were also induced in these treated groups. The number or area of Cx32 positive spots per hepatocyte was significantly decreased in treated groups except for DEN + Oxf 100 ppm group, as compared to DEN alone group. GST-P positive foci was significantly increased in DEN + Fen groups treated with 1800 ppm or more, DEN + Feb groups treated with 1000 ppm Feb or more and DEN + Oxf groups treated with 250 ppm Oxf or more. These results suggest that these three compounds have liver tumor promotion effects and the promoting action in Oxf is most strong among them.

Topics: Administration, Oral; Animals; Anthelmintics; Benzimidazoles; Diethylnitrosamine; Dose-Response Relationship, Drug; Fenbendazole; Guanidines; Liver Neoplasms, Experimental; Male; Rats; Rats, Inbred F344

Topics: Animal Feed; Animals; Animals, Domestic; Anti-Bacterial Agents; Anti-Infective Agents; Benzimidazoles; Cephalosporins; Chlortetracycline; Drug Residues; Fenbendazole; Food Additives; Food Analysis; Guanidines; Ivermectin; Macrolides; Nitriles; Oxytetracycline; Tetracycline; Triazines; Veterinary Medicine

Plasma concentrations of febantel and its major metabolites, fenbendazole, oxfendazole and fenbendazole sulphone, were determined after oral administration of 7.5 mg/kg febantel in lambs before and 28 days after infection with 100,000 L3 larvae of a benzimidazole (BZ)-sensitive or BZ-resistant strain of Ostertagia circumcincta or with 75,000 L3 larvae of a BZ-sensitive Trichostrongylus colubriformis strain. The febantel concentrations were always low, and in only a few samples were higher than the limit of detection. A mean decrease in the area under the curve (AUC) for the three metabolites of 10.2%, 16.4% and 4.9% in lambs infected, respectively, with BZ-sensitive O. circumcincta, BZ-resistant O. circumcincta and T. colubriformis was observed. The Cmax for all the metabolites was higher in the BZ-sensitive O. circumcincta group than in the naive sheep, while the Tmax occurred earlier. The Cmax and the Tmax values for all the metabolites were lower in the BZ-resistant O. circumcincta group than in their own naive controls. In the T. colubriformis group the Cmax values of the metabolites were lower and the Tmax occurred much later.

Topics: Administration, Oral; Animals; Anthelmintics; Benzimidazoles; Drug Resistance; Feces; Fenbendazole; Guanidines; Male; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogens; Sheep; Sheep Diseases; Trichostrongylosis; Trichostrongylus

Plasma concentrations of febantel and its major metabolites fenbendazole, oxfendazole and oxfendazole sulphone were determined after oral administration of 7.5 mg/kg febantel in lambs before and 28 days after infection with 50,000 L3 larvae of Ostertagia circumcincta or Trichostrongylus colubriformis. The febantel concentrations were always very low and only in a few samples higher than the detection limit. The mean decrease in AUC for the three metabolites for the infected sheep in comparison to the parasite naïve sheep was 13.9% +/- 4.1% (mean +/- SEM) and 23.7% +/- 5.3% in the O. circumcincta infected and the T. colubriformis infected lambs respectively. This reduction was only significant for the T. colubriformis infected group. In order to determine a more complete pharmacokinetic profile, febantel was injected intravenously at a dose of 2.5 mg/kg in a further study.

Topics: Administration, Oral; Animals; Anthelmintics; Benzimidazoles; Biological Availability; Chromatography, High Pressure Liquid; Feces; Fenbendazole; Guanidines; Injections, Intravenous; Male; Ostertagiasis; Parasite Egg Count; Sheep; Sheep Diseases; Trichostrongylosis

Topics: Adrenergic beta-Antagonists; Animals; Anthelmintics; Azaperone; Benzimidazoles; Drug Residues; Fenbendazole; Food Analysis; Food Contamination; Guanidines; Promazine; Propanolamines; Spiramycin; Tranquilizing Agents; Tylosin

This report presents the results obtained using 14 anthelmintic compounds that were tested in experimental white mice of the Swiss-Webster strain for their action against Capilaria hepatica. Four of the drugs effectively prevented deposition of C. hepatica ova in mouse liver. The doses at which these four drugs prevented greater than 99% of egg deposition were: albendazole, 30 mg/kg; febantel, 30 mg/kg; mebendazole, 3.13 mg/kg; and oxfendazole, 12.5 mg/kg. Of these, mebendazole is the only agent for which the application of five daily doses of 3.13 mg/kg lay within the dose range recommended for man.

Topics: Albendazole; Animals; Anthelmintics; Benzimidazoles; Capillaria; Guanidines; Liver; Male; Mebendazole; Mice; Nematode Infections; Ovum

Treatment of buffalo calves (Bubalus bubalis) at different times after birth demonstrated that transmission of Toxocara vitulorum from the cow to the calf via milk occurs in all calves during the first 2 days after birth, decreases to 53% by 6 days, 10% by 8-9 days and 2% from Day 10 onwards. This may be because the larvae are no longer in the milk or because the calf has become resistant to the establishment of a new infection. The result also emphasizes the importance of mammary transmission of the parasite. Against immature parasites the efficacy of pyrantel and levamisole was 97%; febantel was 100% on one farm, only 35% on another; piperazine 42% and thiabendazole 35%. Santonin was ineffective in four calves. Against mature parasites the efficacy of pyrantel was 100%; febantel was 100% on one farm, only 35% on another; oral levamisole 83%; cutaneous levamisole 73%; oxfendazole 89%; and piperazine 57%. Nevertheless, piperazine reduced the infection to levels which were probably not pathogenic. In general, the efficacy against mature parasites was similar to that against immature parasites. Treatment of 10-16-day-old calves with an anthelmintic, which is effective against immature parasites, is recommended. This procedure greatly reduces contamination of the environment and also precludes the pathogenic effect of a large number of immature or mature parasites.

Topics: Animals; Anthelmintics; Benzimidazoles; Buffaloes; Female; Guanidines; Levamisole; Milk; Piperazine; Piperazines; Pyrantel; Santonin; Thiabendazole; Time Factors; Toxocariasis

Febantel and one of its main metabolites, febantel sulphoxide, are chemically modified to only a slight extent when incubated in vitro with sheep and cattle ruminal fluids; other major metabolites, fenbendazole and oxfendazole, are respectively, oxidized to oxfendazole and reduced to fenbendazole. Febantel is negligibly metabolized by hepatic cytosol fractions but microsome preparations effect more extensive metabolic transformations. Important differences in this respect were found between microsome preparations from rat, horse, pig, cattle, sheep, chicken and trout livers.

Topics: Animals; Anthelmintics; Benzimidazoles; Biotransformation; Cattle; Chickens; Cytosol; Female; Fenbendazole; Guanidines; Horses; Liver; Male; Microsomes, Liver; Rats; Rats, Inbred Strains; Rumen; Sheep; Species Specificity; Swine; Trout

Topics: Animals; Anthelmintics; Benzimidazoles; Camelus; Guanidines; Kinetics

The pharmacokinetics of febantel and its main metabolites were studied in cattle and sheep. Seven ewes and 4 heifers were given febantel orally in a single dose of 7.5 mg/kg, 25 mg/kg, or 45 mg/kg of body weight. Plasma concentrations vs time of febantel and individual metabolites were determined by high-performance liquid chromatography analysis. Intestinal absorption of febantel was faster and biotransformations were more active in sheep than in cattle.

Topics: Administration, Oral; Animals; Anthelmintics; Benzimidazoles; Cattle; Female; Fenbendazole; Guanidines; Sheep