Fenbendazole Research Articles

Further investigations of the primary mechanism of benzimidazole resistance in Haemonchus contortus

The binding of the [ 3H] benzimidazole carbamates (BZCs)—albendazole (ABZ), oxibendazole (OBZ), parbendazole (PBZ), mebendazole (MBZ), fenbendazole (FBZ) and oxfendazole (OFZ)—to tubulin from three ecologically-related isolates of adult Haemonchus contortus has been examined. The extent of binding of each BZC was inversely proportional to the known resistance status of the isolate. Biochemically, the change in the formation of the BZC-tubulin complex was due to a reduction in the amount of drug bound to resistant tubulin, with no significant change in the association constant of the complex. The resistance factors derived from the binding data support the hypothesis that the complex is ligand-dependent, with the aryl-substituted BZCs—MBZ, OFZ and FBZ—demonstrating lower resistance factors than those of the alkyl-substituted BZCs—ABZ, OBZ and PBZ. Examination of the slope derived from plots of binding against protein concentration demonstrated that the failure of resistant or partially resistant isolates to bind was due to either a decrease in the number of binding sites or, more likely, to reduced stability of the BZC-tubulin complex rendering it unstable to charcoal extraction.

Pharmacokinetics of triclabendazole alone or in combination with fenbendazole in sheep.

Pharmacokinetics of triclabendazole alone or in combination with fenbendazole in sheep.

A field evaluation of oxibendazole in horses infected with benzimidazole resistant small strongyles

Horses with a history of frequent benzimidazole (BZD) treatment were used in a trial to assess the effectiveness of oxibendazole (OBZ). Initial investigations established that these animals were infected with small strongyles resistant to thiabendazole (TBZ), mebendazole (MBZ), cambendazole (CBZ), oxfendazole (OXF) and fenbendazole (FBZ). The herd was subsequently divided into four groups and received TBZ, CBZ, OBZ, or no treatment. OBZ effectly reduced fecal egg counts. Similar reductions were not observed with TBZ or CBZ.

Comparative clinical efficacy of fenbendazole and thiabendazole in feedlot heifers

Heifers shedding eggs of nematodes or Moniezia were treated with either 5 mg/kg fenbendazole (FBZ) or 110 mg/kg thiabendazole (TBZ). 7 days later only trichostrongyle eggs were found (in 2 of 91 FBZ-treated heifers and 10 of 93 TBZ-treated heifers). The feedlot performances (average daily weight gain) were 0.75, 0.82 and 0.81 in the FBZ, TBZ and control groups, resp., over 34 days. The overall incidence of respiratory disease was 84 of 324 heifers used and was about equal in all 3 groups. Mortality was 4, 2 and 3 in the FBZ, TBZ and control groups, resp. Neither anthelmintic improved heifer performance.

Pharmacokinetics of fenbendazole, albendazole and oxfendazole in sheep

Pharmacokinetics of fenbendazole, albendazole and oxfendazole in sheep

Fenbendazole and thiabendazole in cattle: partition of gastrointestinal absorption and pharmacokinetic behaviour.

Fenbendazole (FBZ) and thiabendazole (TBZ) were administered intraruminally with a single dose of an indigestible marker, chromium ethylenediaminetetra-acetate (Cr-EDTA), to cattle fitted with gastrointestinal cannulae. The amounts of anthelmintic leaving the rumen, abomasum and terminal ileum in digesta were derived by compartmental analysis of Cr-EDTA concentrations and integration of benzimidazole concentrations. TBZ was absorbed much more rapidly from the rumen than FBZ and only about 12% of the dose left the rumen in digesta compared with 30% of the FBZ. Approximately 10% and 8% of the TBZ dose appeared at the pylorus and terminal ileum, respectively. Of the above amounts, 9% in the abomasum and practically 100% in the ileum was present as 5-OH-TBZ, indicating that metabolites of absorbed TBZ were recycled to the gastrointestinal tract. Twenty-eight percent and 52% of the FBZ appeared at the pylorus and terminal ileum, respectively, indicating a substantial recycling of absorbed drug to the small intestine. It is suggested that biliary secretion of both TBZ and FBZ and their metabolites may contribute to this recycling. Maximal concentrations of TBZ occurred in plasma in 4 h compared with about 24 h for FBZ. TBZ and metabolites were excreted in urine much more rapidly than were FBZ and metabolites. In plasma and in each of the gastrointestinal compartments, FBZ persisted much longer than did TBZ. It was concluded that slower absorption and excretion and more extensive recycling to the gastrointestinal tract of FBZ, than of TBZ, contribute markedly to its greater potency against helminths.

Speed of actin of some anthelmintics against Dictyocaulus viviparus infection in cattle.

In a study of the comparative speed of action of anthelmintics against Dictyocaulus viviparus infection in cattle levamisole reduced the lungworm burdens by 87 per cent within three hours of administration whereas fenbendazole and febantel required 36 hours to achieve 80 and 87 per cent reduction, respectively. The more rapid action of levamisole may be advantageous in the treatment of bovine parasitic bronchitis since it allows virtually immediate elimination of the majority of the lungworms and limits undesirable sequelae dependent on the continued presence of the parasite.

Prolonged administration: A new concept for increasing the spectrum and effectiveness of anthelmintics

Cambendazole (CBZ), fenbendazole (FBZ), oxfendazole (OFZ) and thiabendazole (TBZ) all inhibited the fumarate stimulated oxidation of NADH in Haemonchus contortus mitochondria. These observations plus the phenomenon of cross resistance to benzimidazoles suggested that the different benzimidazole anthelmintics affect parasitic helminths in a similar manner. The variation in efficiency and spectrum of activity may therefore be due to differences in their pharmacokinetic behaviour. To test this hypothesis, the magnitude and duration of concentrations of TBZ, FBZ and OFZ in plasma and other body compartments after administration were compared with their effectiveness against parasites. The effects of similar doses against benzimidazole-resistant. Trichostrongylus colubriformis and H. contortus were found to correlate with the period high plasma concentrations were maintained. Further evidence of this relationship was obtained by infusion or multiple drenching of TBZ to cattle harbouring arrested Ostertagia ostertagi larvae, so as to maintain high circulating concentrations for an extended period. This resulted in the removal of 90% of the arrested larvae, whereas TBZ as normally administered is considered quite ineffective against these larvae. These observations suggest that the spectrum and effectiveness of benzimidazoles may be improved by extending the period during which parasites are exposed to toxic concentrations.

The effects of benzimidazole resistance and route of administration on the uptake of fenbendazole and thiabendazole by Haemonchus contortus and Trichostrongylus colubriformis in sheep

Abstract Radiolabelled fenbendazole (FBZ) and thiabendazole (TBZ) were administered into the rumen or abomassum of sheep previously infected with benzimidazole-susceptible or resistant Haemonchus contortus and Trichostrongylus colubriformis. Plasma radioactivity was determined for 12 hours following anthelmintic administration and at the end of this time the incorporation of radiolabel into the parasites was determined. Incorporation of radiolabel from FBZ was significantly greater in susceptible than in resistant worms. However, with TBZ there was no significant difference. There were no significant differences in the incorporation between H. contortus and T. colubriformis. Incorporation of TBZ was greater than FBZ in the worms except after ruminal administration to sheep showing clinical parasitism resulting from infection with benzimidazole- susceptible worms. TBZ was administered at five times the dose rate as FBZ, and thus a lower proportion of the administered TBZ than FBZ was incorporated. With the exception of incorporation of TBZ by resistant worms, the route of administration had a major effect on incorporation by the parasites and on plasma levels. Based on plasma levels, TBZ appeared to be rapidly absorbed from both the rumen and abomasum, whereas FBZ was less readily absorbed from the rumen with the rate of absorption being markedly greater if FBZ was administered directly into the abomasum. The findings suggest that the rumen may act as a reservoir of FBZ prolonging the period of high anthelmintic concentration in the host. This may contribute to the high efficacy of this anthelmintic.

Fenbendazole: a new, highly effective anthelmintic.

Fenbendazol wirkt bei einer Dosis von 5 bis 10 mg/kg p.o. auf alle bedeutenden Magen-, Darm-Nematoden inkl. einiger Organnematoden von Schwein, Schaf, Rind und Pferd, wobei nicht nur die Adulten, sondern auch die chemotherapeutisch schwer zu beeinflussenden Entwicklungsstadien (O. ostertagi) praktisch vollstandig eliminiert werden. Bei extrem guter Vertraglichkeit (bis zu 1000fach therapeutischer Dosis) und fehlender teratogener Wirkung konnte hier ein vielversprechendes Anthelminthikum entwickelt werden.