Digoxin-interactions in man: spironolactone reduces renal but not biliary digoxin clearance

Eur J Clin Pharmacol. 1992;42(5):481-5. doi: 10.1007/BF00314854.


The possibility of an inhibitory effect of spironolactone on the biliary clearance of digoxin has been investigated in 6 healthy subjects. Plasma clearance and the renal and biliary clearance of digoxin were determined twice at steady state (digoxin 0.5 to 1 mg.d-1 p.o. for 6 days), alone or in combination with spironolactone 200 mg daily, after an intravenous dose of digoxin (0.7 x oral dose) on Day 7. Plasma and urine were collected for 48 h. Biliary clearance of digoxin was determined on Day 8 by a duodenal perfusion technique. During spironolactone treatment plasma digoxin clearance tended to be lower (255 vs 224 ml/min; P = 0.057) and renal clearance significantly lower (166 vs 144 ml/min), while the biliary clearance of digoxin remained unchanged (106 vs 103 ml/min). Thus, spironolactone reduced the renal clearance of digoxin by an average of 13%, without affecting its biliary clearance.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bile / metabolism
  • Digoxin / administration & dosage
  • Digoxin / blood
  • Digoxin / pharmacokinetics*
  • Digoxin / urine
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Male
  • Metabolic Clearance Rate / drug effects
  • Spironolactone / pharmacology*


  • Spironolactone
  • Digoxin