Influence of amiodarone on oral digoxin bioavailability in healthy volunteers.

The aim of the present work was to evaluate the possible influence of amiodarone on some basic parameters of acute oral digoxin kinetics. A single oral dose of digoxin (0.50 mg) was administered to six healthy volunteers both before and at the end of a 7-day treatment with with amiodarone. This treatment caused a clear-cut rise in peak serum digoxin levels (Cmax) from 2.92 +/- 1.09 to 5.87 +/- 1.68 ng/ml (p less than 0.005) and a decrease of the peak time (Tmax) in four out of the six subjects. The area under the serum concentration-time curve (AUC) was increased by amiodarone with a high individual variability (30.71 +/- 6.15 vs 40.63 +/- 10.04 ng X h X ml-1). Also the 72-hour recovery of the glycoside in the urine was higher (258.77 +/- 68.41 vs 357.62 +/- 62.98 micrograms; p less than 0.01), while renal clearance (Clr) was not altered. These results show that amiodarone increases digoxin bioavailability by a mechanism which appears to be independent of changes in drug elimination.