Influence of ruminal bypass on the pharmacokinetics and efficacy of benzimidazole anthelmintics in sheep

Oxfendazole, fenbendazole and albendazole were each administered at 5 mg kg (-1) to sheep fitted with abomasal cannulae as a single bolus intra-ruminal ly or infused intra-abomasally at a declining exponential rate, with half-l ife equivalent to the rate of rumen fluid outflow. The pharmacokinetic disp osition of parent compound and metabolites in plasma and abomasal fluid was determined by high performance liquid chromatography. Compared with intra- ruminal administration, intra-abomasal infusion of fenbendazole lowered the area under the concentration-time curve of drug in both plasma and abomasa l fluid; intra-abomasal infusion of albendazole substantially increased max imum drug concentration and the concentration-time curve in abomasal fluid and lowered the plasma concentration-time curve of the sulphoxide metabolit e; intra-abomasal infusion of oxfendazole increased maximum concentration a nd the concentration-time curve of drug in plasma and abomasal fluid. The g reater availability in abomasal fluid of oxfendazole and albendazole when g iven at commercial dose rates of 5 mg kg(-1) and 3.9 mg kg(-1), respectivel y, by intra-abomasal infusion correlated with increased efficacy of both dr ugs against benzimidazole-resistant Trichostrongylus colubriformis and of a lbendazole against benzimidazole-resistant Haemonchus contortus over that a chieved by intra-ruminal administration as a single bolus. (C) 1999 Austral ian Society for Parasitology. Published by Elsevier Science Ltd. All rights reserved.