Albendazole

The anthelmintic action of albendazole is thought to be mainly intra-intestinal. However at the higher doses recommended for albendazole, sufficient amounts of albendazole are absorbed and metabolised to the active sulphoxide metabolite, to have a therapeutic effect against tissue parasites including hydatid cysts and cysticerci.

Albendazole exhibits larvicidal, ovicidal and vermicidal activity, and is thought to exert its anthelmintic effect by inhibiting tubulin polymerization. This causes a cascade of metabolism disruption, including energy depletion, which immobilises then kills the susceptible helminth.

Albendazole is effective in the long term treatment of tissue helminth infections, including hydatid disease (echinococcosis), caused by infestation with the tapeworm, Echinococcus granulosus. Albendazole is also effective in the treatment of larval Taenia solium infection (cysticercosis), particularly where there is neurological involvement (neurocysticercosis).

Albendazole therapy has also been used in the short term treatment of a wide range of intestinal helminth infections.

The anthelmintic action of albendazole is thought to be mainly intra-intestinal. However at the higher doses recommended for albendazole, sufficient amounts of albendazole are absorbed and metabolised to the active sulphoxide metabolite, to have a therapeutic effect against tissue parasites including hydatid cysts and cysticerci.

Albendazole exhibits larvicidal, ovicidal and vermicidal activity, and is thought to exert its anthelmintic effect by inhibiting tubulin polymerization. This causes a cascade of metabolism disruption, including energy depletion, which immobilises then kills the susceptible helminth.

In man, the full extent of albendazole absorption following oral administration has not been established. However, it is known that albendazole is poorly absorbed, with most of an oral dose remaining in the gastrointestinal tract. The poor absorption is believed due to the low aqueous solubility of albendazole.

Albendazole rapidly undergoes extensive first-pass metabolism in the liver, and is generally not detected in plasma. Albendazole sulphoxide is the primary metabolite, which is thought to be the active moiety in effectiveness against systemic tissue infections. The plasma half life of albendazole sulphoxide is 8½ hours.

There is wide inter-subject variability in plasma sulphoxide concentrations, which is believed related to differences in absorption rather than differences in metabolism.

Following oral administration of a single dose of 400mg albendazole in fasting patients, the maximum plasma concentration of albendazole sulphoxide occurred approximately 2¼ hours after dosing and ranged from 0.4 to 1.6mmol/L. In patients taking albendazole with breakfast (estimated fat content 40g) the maximum plasma concentration of albendazole sulphoxide ranged from 1.8 to 6.0mmol/L after approximately 3¾ hours. The corresponding area under the curve (AUC) values also increased when albendazole was taken with breakfast, from a median of 4.1 to 20.6 mmol/L.h over the first 8 hours. Large inter-subject variability in AUC values for both the fasting or fed states has been reported.

The systemic pharmacological effect of albendazole is therefore augmented if the dose is administered with a fatty meal, which significantly enhances absorption (approximately 5 fold).

Albendazole sulphoxide and its metabolites appear to be principally eliminated in bile, with only a small proportion appearing in the urine. Elimination from cysts (and possibly from host tissues) has been shown to occur over several weeks following high and prolonged dosing, so that low levels of albendazole sulphoxide may occur in plasma for several weeks.