Chemotherapy of alveolar echinococcosis. Comparison of plasma mebendazole concentrations in animals and man

Abstract

High oral doses of mebendazole have been only partly effective in the treatment of patients with alveolar or cystic echinococcosis. In order to improve therapeutic results the pharmacology of mebendazole has been investigated. Jirds experimentally infected with larval Echinococcus multilocularis were given food containing mebendazole 100 to 1000 ppm. Drug plasma concentrations above 0.25 mumol/l were associated with a reduction in parasite weight to 1 to 10% of that in untreated controls. In treated animals parasite weight was negatively correlated with the plasma mebendazole concentration and with the duration of therapy. In patients on long term therapy with similar doses of mebendazole (16 to 48 mg/kg per day), plasma concentrations were much lower than in jirds. Only 19% of fasting plasma concentrations exceeded 0.25 mumol/l. Plasma concentrations 4 h after the morning dose did not exceed this value in 48% of cases. The results can be explained by the irregular drug absorption and short plasma half life observed in 7 hospitalized patients. It is likely that better results would be obtained if doses of mebendazole were adjusted to produce peak plasma levels exceeding 0.25 mumol/l.