Influence on the antithyroid compound methimazole on the plasma disposition of fenbendazole and oxfendazole in sheep.

The influence of methimazole on the plasma disposition kinetics of fenbendazole, oxfendazole and their metabolites, was investigated in adult sheep. The two anthelmintics were administered by oral drench at 5 mg kg-1 either alone (control treatments) or together with methimazole given orally at 3 mg kg-1. Blood samples were taken serially for 144 hours. Fenbendazole parent drug and its sulphoxide and sulphone metabolites were the three analytes observed by high performance liquid chromatography (HPLC) after the administration of both anthelmintics. The disposition of each analyte followed a similar pattern after the administration of the two anthelmintics alone. Oxfendazole was the main component recovered in plasma between four and 120 to 144 hours after the administration of both anthelmintics either with or without methimazole. A modified pattern of disposition, with significantly higher Cmax and AUC values for fenbendazole parent drug, and a delayed appearance in plasma with retarded Tmax values for the sulphoxide and sulphone metabolites, were the main pharmacokinetic changes observed when the drugs were administered with methimazole.