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

Oxfendazole, fenbendazole and albendazole were each administered at 5mgkg(-1) to sheep fitted with abomasal cannulae as a single bolus intra-ruminally or infused intra-abomasally at a declining exponential rate, with half-life equivalent to the rate of rumen fluid outflow. The pharmacokinetic disposition 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 abomasal fluid; intra-abomasal infusion of albendazole substantially increased maximum drug concentration and the concentration-time curve in abomasal fluid and lowered the plasma concentration time curve of the sulphoxide metabolite; intra-abomasal infusion of oxfendazole increased maximum concentration and the concentration-time curve of drug in plasma and abomasal fluid. The greater availability in abomasal fluid of oxfendazole and albendazole when given at commercial dose rates of 5 mg kg(-1) and 3.9 mg kg(-1), respectively, by intra-abomasal infusion correlated with increased efficacy of both drugs against benzimidazole-resistant Trichostrongylus colubriformis and of albendazole against benzimidazole-resistant Haemonchus contortus over that achieved by intra-ruminal administration as a single bolus.