Prolonged administration: A new concept for increasing the spectrum and effectiveness of anthelmintics

Abstract

Cambendazole (CBZ), fenbendazole (FBZ), oxfendazole (OFZ) and thiabendazole (TBZ) all inhibited the fumarate stimulated oxidation of NADH in Haemonchus contortus mitochondria. These observations plus the phenomenon of cross resistance to benzimidazoles suggested that the different benzimidazole anthelmintics affect parasitic helminths in a similar manner. The variation in efficiency and spectrum of activity may therefore be due to differences in their pharmacokinetic behaviour. To test this hypothesis, the magnitude and duration of concentrations of TBZ, FBZ and OFZ in plasma and other body compartments after administration were compared with their effectiveness against parasites. The effects of similar doses against benzimidazole-resistant. Trichostrongylus colubriformis and H. contortus were found to correlate with the period high plasma concentrations were maintained. Further evidence of this relationship was obtained by infusion or multiple drenching of TBZ to cattle harbouring arrested Ostertagia ostertagi larvae, so as to maintain high circulating concentrations for an extended period. This resulted in the removal of 90% of the arrested larvae, whereas TBZ as normally administered is considered quite ineffective against these larvae. These observations suggest that the spectrum and effectiveness of benzimidazoles may be improved by extending the period during which parasites are exposed to toxic concentrations.