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Digoxin disposition in elderly humans with hypochlorhydria

J Hui¹, D R Geraets, A Chandrasekaran

¹College of Pharmacy, Ohio State University, Columbus 43210.

Journal of Clinical Pharmacology

|July 1, 1994

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Hypochlorhydria, a condition of low stomach acid, alters digoxin (D3) disposition. Reduced stomach acid increases D3 urine excretion and decreases fecal excretion, indicating altered gastrointestinal metabolism.

Area of Science:

Pharmacokinetics
Gastrointestinal Metabolism
Drug Disposition

Background:

Digoxin (D3) metabolism involves gastrointestinal acid hydrolysis and bacterial reduction.
The influence of hypochlorhydria on digoxin disposition requires further investigation.

Purpose of the Study:

To test the hypothesis that hypochlorhydria influences digoxin disposition.
To investigate the impact of reduced stomach acid on digoxin's absorption and metabolism.

Main Methods:

Administered D3 tablets to normochlorhydric (NC) and hypochlorhydric (HC) subjects for 19-28 days.
Collected and analyzed quantitative urine and fecal samples at steady state for D3 and metabolites using HPLC.
Performed in vitro anaerobic cultures of feces and jejunal fluid with D3.

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Main Results:

Urine D3 excretion increased from 37% in NC to 46% in HC (P < .05).
Fecal D3 excretion decreased from 29% in NC to 14% in HC (P < .05).
In vitro bacterial reduction of D3 in fecal incubates was observed, but not consistently predictive of in vivo findings.

Conclusions:

Hypochlorhydria significantly alters digoxin disposition, affecting its urinary and fecal excretion.
Decreased stomach acid hydrolysis and potentially increased intestinal metabolism contribute to altered D3 disposition in HC subjects.
Further research is needed to fully elucidate the metabolic mechanisms of digoxin in hypochlorhydria.