Influence of ruminal bypass on thepharmacokinetics and efficacy of benzimidazoleanthelmintics in sheep

Abstract Oxfendazole, fenbendazole and albendazole were each administered at 5 mg kg −1 to sheep fitted with abomasal cannulae as a single bolus intra-ruminally orinfused intra-abomasally at a declining exponential rate, with half-life equivalent to the rate ofrumen fluid outflow. The pharmacokinetic disposition of parent compound and metabolites inplasma and abomasal fluid was determined by high performance liquid chromatography.Compared with intra-ruminal administration, intra-abomasal infusion of fenbendazole loweredthe area under the concentration–time curve of drug in both plasma and abomasal fluid;intra-abomasal infusion of albendazole substantially increased maximum drug concentration andthe concentration–time curve in abomasal fluid and lowered the plasma concentration–time curveof the sulphoxide metabolite; intra-abomasal infusion of oxfendazole increased maximumconcentration and the concentration–time curve of drug in plasma and abomasal fluid. Thegreater availability in abomasal fluid of oxfendazole and albendazole when given at commercialdose rates of 5 mg kg −1 and 3.9 mg kg −1 , respectively, byintra-abomasal infusion correlated with increased efficacy of both drugs againstbenzimidazole-resistant Trichostrongylus colubriformis and of albendazole againstbenzimidazole-resistant Haemonchus contortus over that achieved by intra-ruminaladministration as a single bolus.