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.
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
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
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
Abdominal discomfort and
diarrhea may occur when the worm load is heavy. Its use is contraindicated
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.