Copyright © 1993 by the European Society of Cardiology.
© 1993 The European Society of Cardiology
Pharmacokinetic and pharmacodynamic profiles of d-sotalol and d,l-sotalol
Clinical Pharmacology Unit, Saint-Antoine University Hospital Paris, France
Correspondence: Dr Ch. Funck-Brentano, Unitéde Pharmacologie Clinique, Hôpital Saint-Antoine, 184 rue du Fbg Saing-Antoine, 75012-Paris, France
d.l-Sotalol is a racemic drug composed of equimolar amounts of d-(+)-sotalol and l-(–)-sotalol. The l-(–)-enantiomer has both beta-blocking (class II) activity and potassium-channel-blocking (class III) properties. The d-(+)-enantiomer has class III properties similar to those of l-sotalol. However, the affinity of d-sotalol for beta-adrenergic receptors is 30 to 60 times lower than the affinity of l-sotalol.
The pharmacokinetics of d,l-sotalol are linear. Following oral administration, absorption and bioavailability are almost complete; apparent elimination half-life ranges from 7 to 18 hours. More than 80% of racemic sotalol elimination occurs by renal excretion of unchanged drug. Sotalol is not metabolized, nor is it significantly bound to plasma proteins. Thus, steadystate plasma concentration is reached within 3 days of treatment onset in patients without renal insufficiency. Dosage of sotalol should be adjusted to creatinine clearance. The pharmacokinetic profile of d-sotalol is similar to that of the racemate.
Plasma concentrations of racemic sotalol associated with beta-adrenergic blockade are similar to those associated with its class III actions. QT interval prolongation with d,l-sotalol is dose- and concentration-dependent and decreases at rapid heart rates. Also, QT interval prolongation at a given plasma concentration during repeated dosing tends to be less pronounced than QT prolongation at the same plasma concentration during single dosing. The class III actions of d-sotalol in the sinus node are associated with slowing of sinus heart rate, whereas additional beta blockade contributes to the decrease in heart rate observed with I- or d,I sotalol. Preliminary studies indicate that racemic sotalol reduces dispersion of repolarization following myocardial infarction. Finally, d-sotalol exerts positive inotropic actions that may disappear in ischemic tissues, whereas d,l-sotalol has a potential to decrease contractility due to its additional beta-blocking properties.
Key Words: Sotalol • potassium channel • class III • enantiomer • antiarrhythmic agent • pharmacokinetics • pharmaco-dynamics