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2064804 
Journal Article 
Flecainide: single and multiple oral dose kinetics, absolute bioavailability and effect of food and antacid in man 
Tjandra-Maga, TB; Verbesselt, R; Van Hecken, A; Mullie, A; De Schepper, PJ 
1986 
Yes 
British Journal of Clinical Pharmacology
ISSN: 0306-5251
EISSN: 1365-2125 
IPA/87/735138 
J 
REF 17 
1986 
eng 
IPA COPYRIGHT: ASHP The kinetics of flecainide acetate (I) after a single intravenous injection of 2 mg/kg and oral administration of 200 mg, absolute bioavailability, and effects of food and aluminum hydroxide (aluminium hydroxide) on I absorption were studied; steady state kinetics following 200 mg twice daily orally for 8 days were determined in 10 healthy subjects. Absolute bioavailability of oral I averaged 70%. Rate and extent of I absorption were not significantly affected by food nor by concomitantly administered aluminum hydroxide. The apparent volume of distribution of 5.5 +- 0.3 l/kg indicates wide distribution of I in tissues. Estimated elimination half-lives from plasma data in the studies averaged 9.3 to 12.4 h (single oral dose studies), 11.8 h (single IV 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 IV dosing CLNR and CLR averaged, respectively, 3.24 +- 0.80 and 2.38 +- 0.49 ml/min/kg. 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, which are well within the therapeutic range.