Author(s): Caldwell JH, Caldwell PB, Murphy JW, Beachler CW
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Abstract Secretion of tritium-labeled digoxin was studied in rats using noneverted gut sacs, in ligated and perfused intestinal preparations in bile duct ligated rats, and by measuring 4 day fecal excretion of total radioactivity in bile duct ligated rats. Serosal to mucosal transfer was proportional to substrate concentration in vitro. In ligated intestinal loops radioactivity was concentrated in the lumen relative to serum. In perfused intestinal preparations the fraction of dose increased with time and was similar over a 100-fold range of doses. Bile duct ligated rats excreted 13.4 +/- 5.8 (S.D.) \% of parenterally administered label in 4 day stool collections. Bile duct ligated rats treated with p.o. activated charcoal excreted significantly more radioactivity (33.4 +/- 7.9\%). The results suggest that net nonbiliary intestinal secretion of digoxin and metabolites can be augmented by intraluminal binding. A role for this phenomenon in accounting for some effects of diseases and drug interactions is suggested.
This article was published in Naunyn Schmiedebergs Arch Pharmacol
and referenced in Journal of Clinical Toxicology