Plasma concentration time course and pharmacological effects of a standardized oral amiodarone dosing regimen in humans.

This study was undertaken to clarify the relationships among dose, plasma concentration time course, therapeutic efficacy, electrocardiographic effects, and toxicity of amiodarone during the initiation and maintenance of oral therapy. A standardized dosing regimen (cumulative dose 10.4 g in the initial two weeks, maintenance dose 400 mg/day, five days per week) was used in eight patients with ventricular arrhythmias. Plasma amiodarone and desethylamiodarone concentrations, electrocardiographic parameters, and selected clinical and laboratory markers of toxicity were monitored at frequent intervals. Arrhythmia control was satisfactory in seven patients. Steady-state plasma amiodarone and desethylamiodarone concentrations (1.7 +/- 1.3 and 1.1 +/- 0.5 microgram/mL, respectively) occurred only after the first month of therapy. In most patients the amiodarone level then remained between 0.5 and 1.0 microgram/mL, but in two it consistently exceeded 2.0 microgram/mL. These were the only patients whose liver function tests became abnormal. Keratopathy and cutaneous photosensitivity were common. No other toxic effects occurred. The heart rate decreased by 20% while the PR interval, QRS duration and QTc interval did not change. The conservative dosing regimen used in this study is therapeutically effective, results in considerable interpatient variation in plasma drug and metabolite concentrations, slows the heart rate without significantly affecting other electrocardiographic parameters, and does not prevent keratopathy, cutaneous photosensitivity or hepatic dysfunction.