Biotransformation and elimination of 14C-flecainide acetate in humans.
The metabolism of 14C-flecainide acetate, a new antiarrhythmic, was investigated in four healthy human subjects, after a single, 200-mg oral dose. The cumulative recovery of radioactivity ranged from 81 to 90% (mean, 86%) in urine and from 4 to 6% (mean, 5%) in feces; thus, flecainide does not appear to undergo extensive biliary excretion, unless reabsorption occurs after biliary elimination. The cumulative excretion in urine of unchanged flecainide ranged from 35 to 50% (mean, 42%) of the dose and was essentially complete by 72 hr postdose. Peak plasma levels of radioactivity (524 to 848 ng eq/ml) and of unchanged flecainide (214 to 281 ng/ml) were attained at 2 to 3 hr postdose. The average half-life for the disappearance of unchanged flecainide from plasma was about 16 hr; disappearance of total metabolites from plasma was only slightly slower. Radiomonitored TLC analysis showed that urine contained two major metabolites and two or three minor ones; both major metabolites were extensively conjugated. By TLC, NMR, and mass spectral comparisons to reference compounds, the two major urinary metabolites were shown to be meta-O-dealkylated flecainide and the meta-O-dealkylated lactam of flecainide. Most of the radioactivity in urine was accounted for by flecainide and the two major metabolites.
D000328:Adult; D001711:Biotransformation; D002855:Chromatography, Thin Layer; D003640:Dealkylation; D005243:Feces / Q000032:analysis; D005260:Female; D005424:Flecainide; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010880:Piperidines / Q000378:metabolism*
D010880:Piperidines; D005424:Flecainide