After oral administration in healthy human subjects, flecainide absorption is prompt (average peak level at 3 to 4 hours) and nearly complete (at least 90%); flecainide does not appear to undergo consequential presystemic biotransformation. Oral absorption in patients with cardiac arrhythmias, renal disease and congestive heart failure (CHF) is also good. Plasma levels of flecainide are proportional to dose within the therapeutic range. Neither food nor antacid affect the extent of flecainide absorption. In healthy subjects, the plasma half-life of unchanged flecainide is relatively long (mean 13 hours after single doses and 16 hours after multiple dosage). For patients with ventricular premature complexes, the half-life is longer (mean 20 hours), and twice-daily oral dosage is effective. The rate of flecainide elimination from plasma may possibly be reduced in older patients. Overall, the plasma pharmacokinetics of flecainide appear to be reasonably linear (not dose- or concentration-dependent). In humans, most (mean 86%) of a single oral dose is excreted in urine as flecainide and its metabolites; only a small portion (mean 5%) is found in feces. Thus, flecainide does not appear to undergo extensive biliary excretion. A substantial portion (mean 27%) of a dose is excreted in urine as unchanged flecainide. Under alkaline urinary conditions, flecainide elimination may be decreased. Only 2 major and 2 or 3 minor metabolites are found in human urine. The 2 major urinary metabolites possess little or no detectable antiarrhythmic activity and are also the major metabolites present in human plasma (primarily conjugated); since free metabolite levels are very low in plasma, metabolites are not likely to contribute any consequential pharmacologic activity. The rate of flecainide elimination from plasma is somewhat slower in patients with moderate renal failure and in patients with CHF than that for healthy persons, and is markedly slower in some patients with end-stage renal disease. Urinary excretion of unchanged flecainide is somewhat less in moderate renal patients and is markedly less in end-stage renal patients, but is not altered in CHF patients. Dosage should be reduced in patients with more severe renal disease and, if indicated, in some CHF patients. Hemodialysis is not an effective means for removal of unchanged flecainide, but does provide more substantial removal of metabolites. Flecainide is not extensively bound (mean 40%) to human plasma proteins in vitro and binding is independent of total drug level.(ABSTRACT TRUNCATED AT 400 WORDS)