Pharmacokinetics of amiodarone after intravenous and oral administration

Pharmacokinetic studies were conducted in four subjects who received 150 mg amiodarone i.v., in nine subjects who received 200 or 400 mg amiodarone p.o., and in four subjects who received the drug by both routes of administration. Amiodarone concentrations were determined by high pressure liquid chromatography. Aminodarone levels after i.v. administration, with one exception, declined biphasically according to a two-compartment model. The decline appeared to be monophasic after p.o. administration with one exception. Plasma levels after p.o. administration varied considerably between subjects. The biologic half-life after p.o. administration (mean 17.1 h +/- S.D.) was higher than that calculated for the second phase after i.v. administration (mean 4.3 h +/- 0.98 S.D.). Total clearance rate during the second phase was within the range 125-288 ml/min after i.v. and 114-473 ml/min after p.o. administration. The apparent volume of distribution in the central compartment after i.v. administration was found to be about 17.0 l and that calculated for the second elimination phase, 77 l, possibly indicating a concentration of the drug in the tissues. The systemic availability of amiodarone varied from 23 to 50% as determined on the basis of of the ratios of areas under p.o. and i.v. serum concentration curves for four subjects.