STEADY-STATE PLASMA-CONCENTRATIONS OF PROPAFENONE - CHIRALITY AND METABOLISM

In a selected group of 86 patients (60 males, 26 females) with symptom atic ventricular arrhythmias, possible interactions between metabolic and chiral effects at steady-state were investigated by comparing the plasma levels of propafenone, its major metabolites and the 2 structur al isomers. The antiarrhythmic drug propafenone is metabolized - besid es a minor dealkylation pathway - mainly via 5-hydroxylation. It is a well-known phenomenon that this oxidative pathway is not shared by all individuals to the same extent. We were able to verify among our subj ects the portion of so-called poor metabolizers reported in the litera ture for the total population. Propafenone was administered as a slow release formulation at 3 different dose regimens (2 x 225 mg, 2 x 325 mg and 2 x 425 mg). The crude drug is a racemic mixture of equal amoun ts of R- and S-forms. During treatment. the plasma S and R ratio was s hifted towards the S-isomer due to preferential clearance of the R-for m. It was further found that neither a genetic disposition (gender, me tabolic phenotype) nor age or the dose applied had any influence on th e measured plasma isomer ratio.