Clinical pharmacology of propafenone: pharmacokinetics, metabolism and concentration-response relations

Abstract

Propafenone is a promising new antiarrhythmic agent marketed in Europe for the past 7 years. The drug is remarkable for great interindividual variability in its pharmacokinetic and pharmacodynamic properties. Propafenone undergoes extensive presystemic clearance that appears to be saturable, with bioavailability increasing as dosage increases. The drug is highly protein bound. Elimination half-life is 5 to 8 hours in most patients, although a range of 2 to 32 hours has been reported. Propafenone slows intracardiac conduction in a concentration-dependent manner. It is a weak beta-adrenergic blocker, but this property is of uncertain clinical significance. The major metabolic pathway for propafenone begins with aromatic ring hydroxylation, a pathway that may be determined by genetic factors.