Studies on the pharmacokinetics and pharmacodynamics of the beta-adrenergic blocking agent sotalol in normal man.

After intravenous injection, sotalol follows a two-compartment distribution pattern. The processes of distribution and elimination are of first order; the intravenous biological half-life is 6 to 8 hours. The drug is mainly excreted by glomerular filtration via the kidney, and metabolites are not found. Of the pharmacodynamic parameters measured, the isoproterenol-induced changes in heart rate, diastolic blood pressure, and free fatty acid return to baseline values immediately during the injection of the beta blocker. Peripheral arterial circulation, lactate, glucose, and pyruvate respond to the beta blocker after a delay. Besides the compartmental distribution of sotalol, other mechanisms of sotalol such as varying responses of the receptors to sotalol or more sluggish intrinsic kinetics of the decrease of parameters measured have to be considered. The effects of various beta blockers may be qualitatively and quantitatively differentiated on the basis of experiments with our test model using steady-state isoproterenol infusion in humans.