DIGOXIN DISPOSITION IN ELDERLY HUMANS WITH HYPOCHLORHYDRIA

Digoxin (D3) metabolism is partially mediated by the gastrointestinal tract via acid hydrolysis of digitoxose sugar moieties and bacterial r eduction of the lactone. The hypothesis that hypochlorhydria influence s digoxin disposition was tested in six normochlorhydric (NC) and four hypochlorhydric (HC) subjects. D3 tablets were administered daily for 19 to 28 days, and quantitative urine and fecal samples were collecte d over the last 3 days (steady state). Samples were analyzed for D3 an d its extractable metabolites by fluorescence-derivatization HPLC. Exc retion of Ds in urine increased from 37% of the dose in NC to 46% in H C, whereas excretion of D3 in feces decreased from 29 to 14%. These ch anges were statistically significant (P < .05) and consistent with dec reased hydrolysis of D3 by stomach acid and increased intestinal metab olism in HC. In each subject, D3 was added to anaerobic cultures of bo th feces and jejunal fluid. Digoxin was reduced in all but two of the fecal incubates, and was not reduced in any jejunal fluid incubates. B ecause dihydrodigoxin (DHD3) was found in only two hypochlorhydric sub jects, in vitro measures of bacterial reduction of D3 were not predict ive of in vivo excretion of reduced metabolites. Sugar-hydrolyzed, red uced metabolites were not found in any subjects. It is concluded that D3 disposition is altered by hypochlorhydria, and that an understandin g of the metabolic mechanisms requires further study.