Pharmacology and efficacy of liposome-entrapped albendazole in experimental secondary alveolar echinococcosis and effect of co-administration with cimetidine.

Encapsulation of the benzimidazole albendazole in multilamellar liposomes results in a preparation in which this normally insoluble anti-hydatid drug is well solublilized in aqueous media. The high entrapment efficiency observed (75-87%) and the stability of the formulation make this a promising delivery vehicle for improved chemotherapy with albendazole. In particular, the high degree of association with phospholipid may give rise to increased oral bioavailability. Oral administration of albendazole in liposomes led to increased concentration and/or altered metabolism of albendazole sulphoxide (ABZSX) in liver and/or plasma in non-infected Wistar rats. Results from experiments using cotton rats (Sigmodon hispidus) infected with metacestodes of Echinococcus multilocularis show that entrapment within liposomes clearly increases the uptake of albendazole via the oral route. This was reflected by increased levels of albendazole and the two major metabolites in plasma, liver and cyst homogenate when a dose of liposomal albendazole (35 mg/kg) was given orally compared to free albendazole at 50 mg/kg. There was a 75-94% reduction in biomass of the metacestode and a significant increase in survival time for the animals treated with liposome entrapped albendazole. A clear difference in distribution of albendazole and its metabolites in the liver and the metacestode tissues in the presence of cimetidine indicated that the latter has a profound effect on the metabolism of albendazole. There appeared to be a synergistic interaction between albendazole and cimetidine, since the metabolism of albendazole was markedly altered in the combined cimetidine/ liposome-albendazole group, and higher therapeutic effect was observed. These findings indicate potential both for improvement of treatment of larval E. multilocularis infection and for reduction of albendazole dose levels.

Initial observation on albendazole in combination with cimetidine for the treatment of human cystic echinococcosis.

Concentrations of albendazole were measured, by high-pressure liquid chromatography, in 19 patients being treated for cystic echinococcosis. All of the patients were given three 4-week courses of albendazole (20 mg/kg/day), separated by 10-day-long drug-free intervals. Seven patients also received three courses of cimetidine (10 mg/kg/day). Concentrations of albendazole sulphoxide (ABZSX) were significantly higher in samples of bile and hydatid cyst fluid from the patients receiving albendazole and cimetidine than in those from patients receiving albendazole alone (P < 0.05). The therapeutic benefit of the combined drug treatment, which was well-tolerated, was more than that with albendazole alone.