Flecainide: single and multiple oral dose kinetics, absolute bioavailability and effect of food and antacid in man

The kinetics of flecainide after single intravenous (2 mg kg-1) and oral (200 mg) dosing, absolute bioavailability, effects of food and aluminium hydroxide on flecainide absorption and steady-state kinetics following twice daily oral dosing (200 mg) have been evaluated in ten healthy subjects. Absolute bioavailability of oral flecainide averaged 70% (range 60-86%). Rate and extent of flecainide absorption were not significantly affected by food nor by concomitantly administered aluminium hydroxide. The apparent volume of distribution of 5.5 +/- 0.3 l kg-1 indicates wide distribution of flecainide in tissues. Estimated elimination half-lives from plasma data averaged 9.3 to 12.4 h (single oral dose studies), 11.8 h (single i.v. dose), and 11.5 h (multiple oral dose). Half-lives calculated from urinary excretion data corresponded well with those calculated from plasma data. Flecainide elimination takes place both by nonrenal (metabolic) clearance and renal excretion of the intact drug involving glomerular filtration and active tubular secretion. Following i.v. dosing CLNR and CLR averaged respectively 3.24 +/- 0.80 and 2.38 +/- 0.49 ml min-1 kg-1. After 200 mg twice daily oral treatment steady state was reached within 3-4 days with trough and peak plasma levels on day 8 of 457 and 662 ng ml-1, which are well within the therapeutic range.