Biliary excretion of digoxin in man

Area of Science:

• Pharmacology
• Gastroenterology
• Hepatology

Background:

• Digoxin is a cardiac glycoside with a narrow therapeutic index.
• Enterohepatic circulation can prolong the action of digoxin.
• Biliary excretion of digoxin has not been well characterized in healthy subjects.

Purpose of the Study:

• To quantify the biliary excretion of 3H-digoxin in normal subjects.
• To assess the potential for reabsorption of excreted digoxin.
• To explore the implications for digoxin pharmacokinetics and toxicity management.

Main Methods:

• Intestinal perfusion techniques were used in normal subjects.
• Minimal interruption of the enterohepatic circulation was ensured.
• Radioactivity of 3H-digoxin in biliary and intestinal fluids was measured.

Main Results:

• Approximately 30% of an intravenous dose of 3H-digoxin was excreted into the digestive tract within 24 hours.
• The majority of excreted radioactivity was chloroform-soluble, indicating potential reabsorption.
• The reabsorbable fraction likely consists of biologically active digoxin.

Conclusions:

• Hepatobiliary excretion is a significant route for digoxin elimination in healthy individuals.
• The enterohepatic circulation of digoxin, via biliary excretion and reabsorption, influences its pharmacokinetics.
• Targeting hepatobiliary function may offer a strategy to manage digoxin intoxication.