Sotalol is an antiarrhythmic agent with combined class II and III properties. It is nearly completely absorbed after oral administration and undergoes essentially no first-pass hepatic metabolism. As a result, its absolute bioavailability is 90-100%. Peak plasma concentrations are reached 2-4 hours after an oral dose. Administering sotalol with food reduces its bioavailability by approximately 20%. A 2-compartment model adequately describes the decline of sotalol plasma concentrations after intravenous or oral administration. The drug has an apparent volume of distribution of 1.2-2.4 liters/kg. Results of animal studies indicate that sotalol distributes into a number of tissues, including those of the heart, liver, and kidney, but it is hydrophilic and thus penetrates the central nervous system poorly. Sotagol does not bind to plasma proteins. No significant biotransformation of sotalol takes place in humans. Sotalol is primarily eliminated by renal excretion, with approximately 80-90% of a dose being excreted unchanged in the urine; a small amount is excreted unchanged in the feces. In subjects with normal renal function, total body clearance of sotalol averages 150 mL/min and the terminal elimination half-life is 10-20 hours. Long-term administration of sotalol does not alter its kinetics, and plasma concentrations following single or multiple doses are proportional to the dose. Sotalol is a racemic mixture of the d-and I-stereoisomers. d,I-Sotalol is excreted in the urine equally as d-and I-sotalol, and there is no evidence of racemization. The clearance of sotalol is reduced and its elimination half-life is prolonged in patients with renal insufficiency; as a result, dosage adjustment is necessary. The elderly exhibit a modest reduction in sotalol clearance that is related to their diminished renal function. There have been no reports of clinically significant pharmacokinetic drug interactions involving sotalol, but pharmacologic interactions may occur. The pharmacologic effects of sotalol are related to its plasma concentrations. Significant [beta] blockade occurs at concentrations [is greater than or equal to] 800 ng/mL, and class III activity has been demonstrated at concentrations as low as 1,200 ng/mL. (AM J Cardiol 1993;72:19A-26A)