Bretylium is a class III antiarrhythmic agent which is used for the management of serious and refractory ventricular tachyarrhythmias. It exhibits a complex pharmacokinetic profile which is poorly understood.The drug is poorly absorbed following oral administration, and its oral bioavailability is in the region of 18 to 23%. Peak plasma concentrations occur at 1 to 9 hours after oral ingestion, and following oral doses of 5 mg/kg average 76 ng/ml, which is 28-fold lower than those achieved after equivalent intravenous doses. Approximately 75% of a bretylium dose is absorbed within 24 hours of intramuscular administration. Peak plasma concentrations occur at 30 to 90 minutes after intramuscular administration and range from 670 to 1500 ng/ml in subjects receiving 4 mg/kg.Bretylium is negligibly bound to plasma proteins (1-6%). Although drug tissue concentrations have not been reported in humans, high values for the apparent volume of distribution suggest extensive tissue binding. In animals, bretylium is progressively taken up by the myocardium over a period of 12 hours, and at 12 hours after bolus administration, myocardial concentrations exceed plasma concentrations 6 to 12 times. It is also avidly taken up by adrenergic nerves in animals.Bretylium is almost entirely cleared by the renal route and its total body clearance is closely correlated with renal clearance. Available data suggest that bretylium exhibits a complex pharmacokinetic profile which has been described by a 3-compartment model in subjects receiving intravenous dosing. The terminal elimination half-life ranges from 7 to 11 hours following oral, intramuscular and intravenous administration, and renal clearance is about 600 ml/min after intravenous administration. About 75% of the dose is recovered in the urine after intravenous dosing.Renal clearance of bretylium is reduced in patients with renal dysfunction, and there is also a significant reduction of the apparent volume of distribution in renal failure. Haemodialysis does not significantly reduce bretylium plasma concentrations.Plasma concentrations are not correlated with bretylium's cardiac actions following single-dose administration. In animals, bretylium exhibits a time- and dose-dependent antiarrhythmic effect which is closely correlated with myocardial but not plasma concentrations. There are few data available from patients receiving long term oral therapy and the therapeutic range has not been defined.Following bretylium administration, transient catecholamine release may produce tachycardia and increased ventricular ectopic activity. The major adverse effect is hypotension, which occurs as a result of the drug's adrenergic blocking action.