Interaction of Fasciola hepatica with albendazole and its metabolites.
Adult Fasciola hepatica recovered from sheep 12 and 24 h after a single oral dose of albendazole (20 mg/kg) contained significant amounts of two oxidized metabolites of albendazole (ABZ), a sulphoxide (SX) and a sulphone (SO), but not ABZ. Flukes incubated in vitro with 10 microM SX or SO contained these metabolites at a level two to three times the level observed in flukes recovered from sheep 24 h after a curative oral dose of ABZ. The concentration of ABZ in flukes was 10-fold greater than either SX or SO after a 24 h in vitro incubation in 10 microM of the respective drug. Flukes exposed to ABZ in vitro contained two-fold higher SX levels than SX-treated flukes due to a combination of spontaneous oxidation in media and fluke-mediated oxidation of ABZ. Measurement of end-products of glucose metabolism following 24 h incubation in 10 microM of either ABZ, SX or SO did not show a significant difference between treated and untreated flukes.
D015766:Albendazole / Q000031:analogs & derivatives; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D002417:Cattle; D005210:Fasciola hepatica / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D010084:Oxidation-Reduction; D012756:Sheep
D000871:Anthelmintics; D001562:Benzimidazoles; D002245:Carbon Dioxide; C027187:albendazole sulfone; D015766:Albendazole; D005947:Glucose; C027186:albendazole sulfoxide