Mechanism of Action of Albendazole
Albendazole exerts its anthelmintic effect by binding to β-tubulin in parasitic cells, which inhibits microtubule polymerization and disrupts essential cellular functions, ultimately leading to parasite death. 1
Primary Mechanism
Albendazole binds specifically to the colchicine-sensitive site of β-tubulin, preventing the polymerization of tubulin dimers into microtubules. 1
The decrease in functional microtubules in intestinal cells of parasites impairs their absorptive function, particularly blocking glucose uptake by both adult and larval forms. 1
Depletion of glucose leads to glycogen storage depletion, resulting in insufficient energy production for adenosine triphosphate (ATP) synthesis, which eventually causes parasite death. 1
Secondary Effects on Parasite Function
Inhibition of microtubule formation disrupts the axoplasmic transport system, which interferes with neuronal activities essential for parasite survival. 2
The antimitotic effects occur in a dose-dependent manner, with higher concentrations producing more pronounced inhibition of microtubule assembly and greater reduction in parasite viability. 2
Disruption of microtubules also affects parasite motility and nutrient uptake, blocking vital processes necessary for survival. 3
Active Metabolite
Albendazole itself is poorly absorbed and rapidly converted in the liver to albendazole sulfoxide, which is the primary active metabolite responsible for systemic anthelmintic activity. 1
The parent compound albendazole is negligible or undetectable in plasma because conversion to the sulfoxide metabolite occurs before reaching systemic circulation. 1
Mechanism of Resistance
- Parasitic resistance to albendazole develops through amino acid changes in the β-tubulin protein, which reduces drug binding affinity to β-tubulin. 1
Important Clinical Consideration
- Albendazole demonstrates activity against larval forms of Echinococcus granulosus and Taenia solium in approved indications, with the mechanism involving the same β-tubulin binding and microtubule disruption. 1