Pharmacotherapeutic group: Anthelmintic.
Pharmacology: Pharmacodynamics: Mechanism of action: Albendazole is a benzimidazole carbamate anthelmintic drug similar to mebendazole. It is a broad-spectrum anthelmintic, which is highly effective against a wide range of intestinal helminths including a variety of intestinal nematodes, cestodes, and trematodes. It is also effective against tissue helminth infections, such as cutaneous larva migrans and has also been used in the high dose, long term treatment of tissue helminth infections including hydatid cysts and cysticercosis.
The anthelminthic action of albendazole is thought to be mainly intra-intestinal due to low absorption (less than 5%) after oral administration. However, at higher albendazole doses, sufficient amount is absorbed and metabolised to the active sulfoxide metabolite, to have a therapeutic effect against tissue parasites.
Albendazole exhibits larvicidal, ovicidal and vermicidal activity, and is thought to act via inhibition of tubulin polymerization. This causes a cascade of metabolic disruption, including energy depletion, which immobilizes and then kills the susceptible helminth.
Pharmacokinetics: Absorption: In man, the full extent of albendazole absorption following oral administration has not been established. However, it is known that albendazole is poorly absorbed (<5%) with most of an oral dose remaining in the gastrointestinal tract. The poor absorption is believed to be due to the low aqueous solubility of albendazole. Absorption is significantly enhanced (up to 5 fold) if albendazole is administrated with a fatty meal compared with fasted state.
Metabolism: Albendazole rapidly undergoes extensive first-pass metabolism in the liver, and is generally not detected in plasma or in urine. Albendazole sulfoxide is the primary metabolite, which is thought to be the active moiety in effectiveness against systemic tissue infections (anthelminthic activity). Peak plasma concentrations of albendazole sulfoxide attained 2 - 5 hours after a dose. Albendazole
sulfoxide is further metabolized to albendazole sulfone and other primary oxidative metabolites.
Distribution: Albendazole sulfoxide is widely distributed throughout the body including into urine, bile, liver, cyst wall, cyst fluid, and cerebrospinal fluid (CSF). It is about 70% bound to plasma protein.
Elimination: Albendazole sulfoxide and its metabolites appear to be principally eliminated in bile, with only a small proportion (<1% of albendazole sulfoxide) appearing in the urine. The plasma half-life of albendazole sulfoxide is 8 - 12 hours.
Special populations: Patients with extrahepatic obstruction: Increased albendazole sulfoxide serum concentration and prolonged half-life. Elimination half-life may be 31.7 hours.