Differences in the metabolism of epicainide in rats and man

Abstract

1. Epicainide is a new potent antiarrhythmic agent, metabolized differently in rats and man.

2. In rats, the aromatic part of the molecule (the two phenyl rings linked to the quaternary carbon atom) undergoes metabolic attack by the mono-oxygenases. The hydroxy and methoxy-hydroxy metabolites are predominant and are excreted in urine and bile both as free and conjugated forms.

3. In contrast, the aromatic moiety of epicainide remains unchanged in man. It is the ethylpyrrolidine ring which is mainly attacked, resulting in the expected N-deethylation, subsequent oxidation of the pyrrolidine moiety, and reduction or hydrolysis of the amide function.

4. A preliminary kinetic analysis of epicainide -in man reveals a linear open 2-compartment model. The radioactivity recoveries confirm the absence of any accumulation of the drug in the organism.