The concentrations of amiodarone (Cordarone) and desethylamiodarone in plasma after single oral and intravenous and long-term oral dosing were determined in seven normal subjects and 106 patients with various cardiac arrhythmias, respectively, using a high-performance liquid chromatographic method. The decline in amiodarone plasma concentration after a single intravenous 400 mg dose was described by a triexponential decay equation, with a mean terminal half-life (t1/2) of 34.5 h. Model independent parameters were calculated from the fits. Mean values for clearance and apparent volume of distribution were 14.7 +/- 7.2 l/h and 376 +/- 372 l. Following single oral doses of 400 mg, amiodarone plasma concentration time data were fitted in a triexponential function. The mean terminal half-life for amiodarone after oral dosage was 31.6 +/- 21.3 h. Amiodarone peak concentrations of 0.37 +/- 0.22 micrograms/ml were attained in 4.8 +/- 1.5 h. The bioavailability of oral amiodarone was only 31 +/- 26%, in part due to first-pass metabolism. Desethylamiodarone , the major metabolite of amiodarone, was present in plasma in very low levels of about 10 ng/ml in several volunteers after single intravenous or oral administration of amiodarone. The mean plasma amiodarone and desethylamiodarone levels in 106 patients, using a mean oral daily maintenance dosage of 440 +/- 253 mg for a mean period of 9.1 months, were 1.85 +/- 1.17 micrograms/ml and 1.35 +/- 0.71 micrograms/ml, respectively. The relationship between the steady state amiodarone and desethylamiodarone plasma concentrations and daily amiodarone maintenance dose in mg in 106 patients was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)