Pharmacokinetic disposition of benzimidazole drugs in the ruminant gastrointestinal tract.
Orally administered benzimidazole (BZ) drugs are ideally deposited in the rumen where they associate extensively with particulate digesta material, the residence time of this drug-digesta complex being a major influence on the subsequent rate and duration of BZ availability. This duration is shortened if the dose should bypass the rumen due to oesophageal groove closure. Benzimidazole metabolites flow from the rumen primarily in association with particulate digesta. In the abomasum, the majority of soluble metabolites result from gastric secretions. These metabolites flow into the small intestine where they are absorbed into the systemic circulation. Depending on the chemical structure a significant portion are secreted in bile either in a free (ie. unconjugated) or conjugated form. Free biliary metabolites are absorbed from the upper small intestine whereas bacteria in the large intestine hydrolyse the conjugated biliary metabolites to promote further absorption. Biliary derived metabolites are enterohepatically recycled but contribute little to the peripheral plasma metabolite pool. In this review, Des Hennessy discusses these issues in relation to the pharmacology of BZ drugs in the gastrointestinal tract of ruminants.
CSIRO Division of Animal Health, McMaster Laboratory, Private Bag No. 1, Glebe, NSW 2037, Australia.
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