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 × 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.
Key words Digoxin - Spironolactone - drug interaction - biliary clearance - pharmacokinetics