Abnormal pharmacokinetics of flecainide in a "nonresponder"

Flecainide is well absorbed after oral administration. Following rapid infusion of flecainide, there is a short distribution phase. Plasma levels of flecainide are proportional to dose. Both QRS durations and flutter wave intervals are lengthened after flecainide administration. We report an abnormal pharmacokinetic response to oral as well as intravenous flecainide in a patient who was treated with flecainide for several episodes of atrial flutter. In contrast to the usual pattern, this patient did not show a significant increase in QRS duration, flutter wave interval, or plasma concentration. We could not explain this abnormal pharmacokinetic response, but excluded a rapid and complete renal clearance, an excessively high rate of metabolization, and an abnormal binding mechanism as possible mechanisms. We concluded that flecainide may produce abnormal pharmacokinetic mechanisms, preventing appearance of unbound substance in plasma, thereby preventing occurrence of electrophysiological effects.