A 24 h intravenous dosing regimen of amiodarone was designed to reach a peak plasma concentration at 1 h and to maintain the concentration above a certain level during the infusion period. A randomized, open-label, digoxin-controlled study was undertaken to observe the efficacy and safety of the dosing regimen of amiodarone in treating recent-onset, persistent, atrial fibrillation and flutter with ventricular rates above 130 beats.min-1. Fifty patients with a mean age of 70 +/- 7 (SD) years were enrolled and randomly assigned to receive either amiodarone intravenously (n = 26) or digoxin (n = 24). Amiodarone HCl was infused over 24 h according to the following regimen: 5 mg.min-1, 3 mg.min-1, 1 mg.min-1 and 0.5 mg.min-1 for 1, 3, 6 and 14 h, respectively, for a 70-kg subject. Digoxin (0.013 mg.kg-1) was infused in three divided doses, each dose 2 h apart and infused over 30 min. The mean heart rates in the amiodarone group decreased significantly from 157 +/- 20 beats.min-1 to 122 +/- 25 beats.min-1 after 1 h (P < 0.05 vs baseline), and then decreased further to stabilize at 96 +/- 25 beats.min-1 after 6 h (P < 0.05). The digoxin group had fewer dramatic alterations in heart rates, compared to the amiodarone group, in the first 8 h (P < 0.05, respectively). Maximum reduction was reached only after 8 h. The amiodarone infusion was prematurely aborted in two patients due to severe bradycardia and death after conversion in one patient and aggravation of heart failure in the other.(ABSTRACT TRUNCATED AT 250 WORDS)