Amiodarone-digoxin interaction. Clinical and experimental observations

Twenty-two patients were given amiodarone for refractory cardiac arrhythmias, and pre- and post-amiodarone serum digoxin levels were studied. The interval between pre- and post-amiodarone serum digoxin levels ranged from five days to nine months (mean interval, seven weeks). The mean (+/- SD) pre-amiodarone serum digoxin level was 1.0 +/- 0.4 ng/ml, and the post-amiodarone serum digoxin level was 1.9 +/- 0.8 ng/ml (p less than .001). To develop an animal model for study of the digoxin-amiodarone interaction, 18 pigs were given digoxin for a four-week period. Half of the animals were given amiodarone as well as digoxin for the last two weeks of the study. At the end of the initial two-week period, there was no difference in serum digoxin levels between the two groups. At the end of the second two-week period, the serum digoxin level in the group receiving digoxin alone was 0.6 +/- 0.2 ng/ml, and the serum digoxin level in the group receiving the digoxin and amiodarone was 1.2 +/- 0.6 ng/ml (p less than .01). These data confirm the presence of an amiodarone-digoxin interaction in man and show that the pig is an appropriate model for study of this clinical phenomenon in the animal laboratory.