Pharmacology, pharmacodynamics and pharmacokinetics of sotalol

Abstract

Sotalol is a nonselective, water-soluble β-adrenoceptor antagonist with no membrane-stablizing activity or intrinsic sympathomimetic activity. Sotalol is, essentially, completely absorbed and is not metabolized. Consequently, bioavailability is close to 100%. Age and food have slight but unimportant effects on bioavailability. C max of sotalol is 2 to 3 hours with a t 1 2 between 7 and 15 hours. Excretion of sotalol is primarily through the kidneys, with no metabolism by liver and no first-pass effect. Therefore, sotalol plasma levels and half-life are directly related to creatinme clearance and glomerular filtration rate. Appropriate dose adjustments must be made for patients with impaired renal function or increased renal blood flow, as in pregnancy. The β-adrenoceptor antagonistic effects of sotalol are directly related to plasma levels, which, in turn, are directly related to dose. However, the β-adrenoceptor antagonism t 1 2 is longer than the sotalol plasma t 1 2 . As a consequence of its ability to prolong the action potential duration, sotalol also increases cardiac contractility in isolated ventricular, but not atrial, preparations by 20 to 40%. This positive inotropic effect is not blocked by β or α blockade or reserpine pretreatment and seems to be related to sotalol's effects on cardiac ionic currents. Like the effects of sotalol on action potential duration, the positive inotropic effects are inversely proportional to rate. The hemodynamics of sotalol indicate a relative lack of direct cardiac depressant activity in both animals and humans. The typical hemodynamic effects of sotalol in normotensive humans, even with depressed myocardial function, are a reduction in heart rate with little or no change in blood pressure, a reduction in cardiac output with no change in stroke volume, and little or no change in pulmonary wedge pressure and left ventricular end-diastotic pressure or volume, and little or no change in ejection fraction either at rest or during exercise.