THE INFLUENCE OF A HEAVY INFECTION WITH SENSITIVE AND RESISTANT STRAINS OF OSTERTAGIA-CIRCUMCINCTA AND WITH TRICHOSTRONGYLUS-COLUBRIFORMIS ON THE PHARMACOKINETICS OF FEBANTEL IN LAMBS

Plasma concentrations of febantel and its major metabolites, fenbendaz ole, oxfendazole and fenbendazole sulphone, were determined after oral administration of 7.5 mg/kg febantel in lambs before and 28 days afte r infection with 100 000 L3 larvae of a benzimidazole (BZ)-sensitive o r BZ-resistant strain of Ostertagia circumcincta or with 75 000 L3 lar vae of a BZ-sensitive Trichostrongylus colubriformis strain. The feban tel concentrations were always low, and in only a few samples were hig her than the limit of detection, A mean decrease in the area under the curve (AUG) for the three metabolites of 10.2%, 16.4% and 4.9% in lam bs infected, respectively with BZ-sensitive O. circumcincta, BZ-resist ant O. circumcincta and T. colubriformis was observed. The C-max for a ll the metabolites was higher in the BZ-sensitive O, circumcincta grou p than in the naive sheep, while the T-max occurred earlier. The C-max and the T-max values for all the metabolites were lower in the BZ-res istant O. circumcincta group than in their own naive controls. Ln the T. colubriformis group the C-max values of the metabolites were lower and the T-max occurred much later.