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Related Experiment Videos

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
PubMed
Summary

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.

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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.