The benzimidazoles are a large chemical family used to treat nematode and trematode infections in domestic animals. They also have limited activity against cestodes. However, with the widespread development of resistance and the availability of more efficient and easier to administer compounds, their use has decreased in ruminants. They are characterized by a broad spectrum of activity against roundworms (nematodes), an ovicidal effect, and a wide safety margin. Those of interest are mebendazole, flubendazole, fenbendazole, oxfendazole, oxibendazole, albendazole, albendazole sulfoxide, thiabendazole, thiophanate, febantel, netobimin, and triclabendazole. Netobimin, albendazole, and triclabendazole are also active against liver flukes; however, unlike all the other benzimidazoles, triclabendazole has no activity against roundworms. Because most benzimidazoles are sparingly soluble in water, they are generally given PO as a suspension, paste, or bolus, although topical formulations have also been developed. Differences in the rate and extent of absorption from the GI tract depend on such factors as species, dosage, formulation, solubility, and operation of the esophageal groove reflex. Flubendazole and fenbendazole are also available as an oral suspension or emulsion for application through drinking water, for administration to pigs and chickens.
The most effective of the group are those with the longest half-life, such as oxfendazole, fenbendazole, albendazole, and their prodrugs, because they are not rapidly metabolized to inactive products. Effective concentrations are maintained for an extended period in the plasma and gut, which increases efficacy against immature and arrested larvae and adult nematodes, including lungworms.
They are more effective in ruminants and horses, in which their rate of passage is slowed by the rumen or cecum. Because the nature of their antiparasitic action depends on prolongation of contact time, repeated (2–3 times) PO administration of a full dose at 12-hr intervals increases their efficacy, even against benzimidazole-resistant worms. In addition, a reduced feed intake, which reduces the flow rate of digesta, increases the availability of benzimidazoles.
In the case of oxfendazole, and probably other benzimidazoles, the major route of exposure is biliary metabolites, followed by enterohepatic recycling of the drug after absorption from the small and large intestine. Worms in the mucosa of the small intestine may be exposed to more recycled anthelmintic than to drug contained in the passing ingesta in the GI tract.
In ruminants, PO treatment with the benzimidazoles removes most of the major adult GI parasites and many of the larval stages. The relative rates of oxidation in the liver and reduction in the GI tract vary between cattle and sheep, with the metabolism and excretion of benzimidazole compounds being more extensive in cattle than in sheep. Consequently, the systemic anthelmintic activity of most benzimidazoles is greater in sheep than in cattle, and dose rates in cattle are often higher than those in sheep. Albendazole, fenbendazole, oxfendazole, and febantel are active against inhibited fourth-stage larvae of Ostertagia spp; however, inconsistent efficacy has been reported. Efficacy against Dictyocaulus viviparus has also been noted for these insoluble benzimidazoles. Oxfendazole, albendazole, and febantel are minimally teratogenic in sheep, whereas fenbendazole, mebendazole, and oxibendazole are not. An oxfendazole pulse-release bolus for intraruminal use has been developed for cattle in Europe; five or six therapeutic doses of oxfendazole (750 or 1,250 mg/tablet) are released approximately every 3 wk in the rumen. A sustained-release fenbendazole bolus is also available for cattle in some European countries; it contains 12 g fenbendazole and has a continual release profile of >140 days. An albendazole slow-release capsule has been marketed in Europe and Australasia for small ruminants. This device contains 3.85 g of albendazole and delivers a daily dose of 36.7 mg for 105 days. It is an efficient device to control benzimidazole-susceptible nematodes. It may also prevent infection with benzimidazole-resistant larvae but does not reduce existing infections.
In cattle and sheep, triclabendazole at 10 mg/kg, PO, is highly effective against immature Fasciola hepatica in the liver parenchyma and against the mature stage in the bile ducts. Albendazole and netobimin at 20 mg/kg are active against mature F hepatica; the other benzimidazoles and probenzimidazoles used for nematode control have only a marginal efficacy against liver flukes. Because of the lack of efficacy against the immature stages, only triclabendazole is indicated for treatment of acute fascioliosis. However, triclabendazole resistance has been reported in several countries. Triclabendazole is not approved for use in ruminants in the USA.
Benzimidazoles also have some anthelmintic activity against Moniezia spp in sheep and cattle.
In horses, the benzimidazoles are characterized by effective removal (90%–100%) of almost all mature strongyles, but third- and fourth-stage larvae are more difficult to eliminate. High levels and repeated administration may be necessary for extra-intestinal migrating stages of large strongyles and for small-strongyle larvae embedded or encysted in the wall of the intestine. However, widespread resistance to benzimidazoles in cyathostome nematodes of horses limits their usage. Repeated doses are thought to be advantageous, because the lethal effect of benzimidazoles is a slow process—hence, their recent incorporation into feed supplements. Ascarid removal in horses varies with various members of the benzimidazole group. Activity against Strongyloides westeri varies also, but Oxyuris equi is usually removed by any of the benzimidazoles at the recommended dose.