Pharmacokinetics of amiodarone in man

Abstract

We studied the kinetics of amiodarone in three healthy volunteers after single oral (400 mg) and intravenous (150 mg) doses and in six patients with supraventricular tachycardia. Three patients were studied after the first oral dose (400 mg) and during subsequent therapy (200 mg/day); the other three after 5 mg/kg of amiodarone intravenous. Blood was drawn at intervals for 24 h in patients and up to 32 h (i.v.) and 50 h (p.o.) from healthy volunteers. The drug was measured by high pressure liquid chromatography (HPLC). No difference in kinetic parameters was found between healthy subjects an patients. The pharmacokinetic parameters, calculated on the intravenous data using a two-compartment open model, indicate a very large volume of distribution (9.26-17.17 L/kg in healthy volunteers and 6.88-21.05 L/kg in patients). The elimination half-life ranged from 12.09 to 20.70 h in volunteers and from 11.60 to 19.60 h in patients. Oral absorption was slow an erratic, with fourfold individual variations in systemic bioavailability (22-86%). A slight accumulation of amiodarone was observed in patients under chronic treatment.