[Pharmacokinetics of four benzimidazoles administered intragastrically to mice infected with secondary cysts of Echinococcus granulosus]

Abstract

Mice infected with secondary cysts of Echinococcus granulosus were treated ig with mebendazole (Meb), albendazole (Alb), albendazole sulfoxide (AlbSO) or albendazole sulphone (AlbSP) at equal effective dosage. The blood concentrations-time courses of the four drugs were adequately fitted to a liner one-compartment open model analysed with a modified NONLIN program, and the major pharmaco- kinetic parameters were then calculated (Table 1). When Alb was given ig to the infected mice, 76.2-84.5% of the drug absorbed was metabolized to AlbSO. There fore, the pharmacokinetics of AlbSO in Alb group was determined. After ig administration of Meb to the infected mice, the ratio of the drug contents in cyst wall to corresponding plasma concentrations of Meb was 10.6-26.9%, but much less in cyst fluid. In Alb and AlbSO groups, similar AlbSO contents in cyst wall and cyst fluid with higher ratio to plasma concentrations were observed (Fig 3). The results suggest that E granulosus cysts were more susceptible to Meb than to Alb or AlbSO, and improvement of Meb absorption would be favourable for enhancement of efficacy in the treatment of hydatid disease.