Pharmacokinetics of amiodarone after intravenous and oral administration

Summary

Seven patients with cardiac arrhythmias were given amiodarone 400 mg intravenously over 2 min, and 2–4 days later the same dose was given orally. The serum concentration of amiodarone was determined by HPLC; the sensitivity of the analysis was 0.1 µg/ml. The time sequence of the measurements of drug concentration made conventional compartemental analysis impossible. There was large individual variation but some of the curves suggested enterohepatic circulation. The time from oral intake to the peak serum concentration was estimated to be 7.3±2.9 h (SD). The “amount of drug reaching the general circulation in 24 h after oral intake” averaged 42% (22–80%). After oral administration of amiodarone 200 mg 8 hourly the serum concentration before the morning dose averaged 0.61 µg/ml after 24 h, 0.76 after 48 h, 1.18 after 1 week and 1.56 µg/ml after 1 month. In one patient, who had been on amiodarone therapy for 8 months, the drug was discontinued and the serum concentration was followed over the next 3 months. The drug elimination curve suggested an elimination half life of 13.7 days. Because of instability in physiological saline protein binding could not be precisely quantitated, but only characterized as strong. No unchanged amiodarone was found in urine. The urinary excretion of iodine over 2 h after intravenous administration suggested that 5% of orally administered amiodarone was eliminated in the urine after biotransformation. No effect of the drug was observed during the first 10 days of treatment. In 2 patients with supraventricular arrhythmia, an excellent response was seen, and in one with ventricular arrhythmia there was a good response.