Several benzimidazoles are in use for the treatment of helminthic infections. Three of these, mebendazole, thi-abendazole and albendazole, are described in this sec-tion. They have a broad range of activity against many nematode and cestode parasites, including cutaneous larva migrans, trichinosis, disseminated strongyloidiasis, and visceral larva migrans. A fourth, triclabendazole, is considered as the drug of choice for Fasciola hepatica therapy.
Thiabendazole (Mintezol) inhibits fumarate reductase and electron transport–associated phosphorylation in helminths. Interference with ATP generation decreases glucose uptake and affects the energy available for me-tabolism. Benzimidazole anthelmintics as a class (e.g., thiabendazole, mebendazole, and albendazole), bind se-lectively to -tubulin of nematodes (roundworms), ces-todes (tapeworms), and trematodes (flukes). This in-hibits microtubule assembly, which is important in a number of helminth cellular processes, such as mitosis, transport, and motility.
Thiabendazole is administered orally and is rapidly absorbed from the intestinal tract, with peak plasma levels achieved in 1 to 2 hours. The drug is metabolized in the liver and excreted in urine within 24 to 48 hours as glucuronide and sulfate esters. Approximately 10% is found in feces.
Thiabendazole shows a broad spectrum of activity against the following nematodes: A. lumbricoides, N. americanus, A. duodenale, E. vermicularis, S. stercoralis, and Trichuris trichiura (whipworm). It has largely been replaced with safer drugs for all but Strongyloides spp. At present, thiabendazole is the drug of choice for the treatment of cutaneous larva migrans (creeping erup-tion), strongyloidiasis, trichostrongyliasis, and trichinosis.
Anorexia, nausea, vomiting, drowsiness, and vertigo occur in up to one-third of patients. Diarrhea, pruritus, rash, hallucinations, crystalluria, and leukopenia are less common; shock, hyperglycemia, lymphadenopathy, and Stevens-Johnson syndrome are rare. Some patients re-port that their urine smells like asparagus, a reaction re-lated to excretion of the metabolite asparagine.
Unlike thiabendazole, mebendazole (Vermox) does not inhibit fumarate reductase. While mebendazole binds to both mammalian and nematode tubulin, it exhibits a differential affinity for the latter, possibly explaining the selective action of the drug. The selective binding to nematode tubulin may inhibit glucose absorption, lead-ing to glycogen consumption and ATP depletion.
Mebendazole is given orally; it is poorly soluble, and very little is absorbed from the intestinal tract. About 5 to 10%, principally the decarboxylated derivatives, is recovered in the urine; most of the orally administered drug is found in the feces within 24 hours.
Mebendazole is used primarily for the treatment of A. lumbricoides, T. trichiura, E. vermicularis, and hook-worm infections, in which it produces high cure rates. It is an alternative agent for the treatment of trichinosis and visceral larva migrans. Owing to its broad-spectrum anthelmintic effect, mixed infections (ascariasis, hook-worm infestation, or enterobiasis in association with trichuriasis) frequently respond to therapy. High doses have been used to treat hydatid disease, but albenda-zole is now thought to be superior.
Abdominal discomfort and diarrhea may occur when the worm load is heavy. Its use is contraindicated during pregnancy.
Albendazole appears to cause cytoplasmic microtubu-lar degeneration, which in turn impairs vital cellular processes and leads to parasite death. There is some ev-idence that the drug also inhibits helminth-specific ATP generation by fumarate reductase.
Albendazole is given orally and is poorly and vari-ably absorbed ( 5%) because of its poor water solubil-ity. Oral bioavailability is increased as much as five times when the drug is given with a fatty meal instead of on an empty stomach. Concurrent treatment with corti-costeroids increases plasma concentrations of albenda-zole. The drug is rapidly metabolized in the liver to an active sulfoxide metabolite. The half life of the metabo-lites is 8 to 12 hours.
Albendazole has a broad spectrum of activity against intestinal nematodes and cestodes, as well as the liver flukes Opisthorchis sinensis, Opisthorchis viverrini, and Clonorchis sinensis. It also has been used successfully against Giardia lamblia. Albendazole is an effective treat-ment of hydatid cyst disease (echinococcosis), especially when accompanied with praziquantel. It also is effective in treating cerebral and spinal neurocysticercosis, particu-larly when given with dexamethasone.Albendazole is rec-ommended for treatment of gnathostomiasis.