Pharmacokinetic evaluation of the digoxin-amiodarone interaction

Paul E. Fenster, Neal W. White, Christine D. Hanson

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Amiodarone is known to raise serum digoxin levels. This study was designed to evaluate the pharmacokinetic basis of this interaction in 10 normal subjects. The pharmacokinetic variables for digoxin were determined after a 1.0 mg intravenous dose of digoxin in each subject, before and after oral amiodarone, 400 mg daily for 3 weeks. During amiodarone administration, systemic clearance of digoxin was reduced from 234 ± 72 ml/min (mean ± standard deviation) to 172 ± 33 ml/min (p < 0.01). This was due to reductions in both renal clearance (from 105 ± 39 to 84 ± 15 ml/min) (p < 0.05) and nonrenal clearance (from 130 ± 38 to 88 ± 20 ml/min) (p < 0.01). Digoxin half-life of elimination was prolonged from 34 ± 13 to 40 ± 16 hours (p < 0.05). Digoxin volume of distribution was not significantly changed. Amiodarone caused a three- to fivefold increase in serum reverse triiodothyronine levels, but changes in thyroid function were not quantitatively related to the changes in digoxin pharmacokinetics. These alterations in digoxin pharmacokinetics produced by amiodarone explain the increase in serum digoxin level that has been observed when this drug combination has been used clinically.

Original languageEnglish (US)
Pages (from-to)108-112
Number of pages5
JournalJournal of the American College of Cardiology
Issue number1
StatePublished - 1985

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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