Pharmacokinetic and pharmacodynamic profiles of d-sotalol and d,l-sotalol.
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, steady-state 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 l- or d,l sotalol.(ABSTRACT TRUNCATED AT 250 WORDS)
Funck-Brentano
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Clinical Pharmacology Unit, Saint-Antoine University Hospital, Paris, France.
D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D013015:Sotalol / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D013015:Sotalol