Thiabendazole (PDF Version)

Class:

Thiabendazole is a benzimidazole carbamate based on a bicyclic ring structure in which a benzene ring is fused to the 4- and 5- positions of an imidazole ring.

Antiparasitic Activity:

Thiabendazole is active against most intestinal nematodes that infect humans,

Mechanism of Action:

Benzimidazoles selectively bind to nematode ß-tubulin, inhibiting polymerization, thus preventing the formation of microtubules and so stopping cell division. Impaired uptake of glucose, leading to depletion of glycogen, and reduced stores of ATP has also been noted. Thiabendazole has been shown to inhibit the helminth-specific enzyme, fumarate reductase.

Mechanism of Resistance:

Resistance to benzimidazoles has been attributed to specific amino acid changes in the ß-tubulin protein, leading to reduced binding affinity for ß-tubulin.

Pharmacokinetics:

Plasma concentrations of thiabendazole peak within 1 to 2 hours of oral administration with most of the drug cleared from the plasma within 8h. Thiabendazole is extensively metabolized in the liver to 5-hydroxythiabendazole before being excreted principally as glucuronide or sulfate conjugates of 5-hydroxythiabendazole. Within 48 hours, 87% of an oral dose of thiabendazole is excreted in urine and 5% in faeces.

Dosage:

The dose of thiabendazole is determined by weight, but some treatment regimens are parasite-specific (Table 3).

Adverse Effects:

Minor. Those most frequently encountered include anorexia, nausea, vomiting, diarrhoea, headache, and dizziness.

Pregnancy:

Risk unknown. Human studies inadequate.

Drug Interactions:

Co-administration of thiabendazole in patients taking theophylline can result in an increase in theophylline levels of greater than 50%.

Brand names/manufacturer:

Mintezol (Merck)