Metabolic studies on the new fasciolicidal drug, closantel

Studies of the metabolic disturbances caused in Fasciola hepatica by closantel have been carried out in vitro and in fluke recovered from treated sheep. Fluke exposed to the anthelmintic under both conditions exhibit increased carbohydrate mobilisation, increased end-product formation, especially of succinate, diminished ATP synthesis, increased oxaloacetate/malate ratios, and increased internal concentrations of pyruvate. No specific enzyme inhibition was detected. These results are consistent with the view that closantel acts as an uncoupler of oxidative phosphorylation by increasing mitochondrial permeability.