Faculty Collaboration Database

Electrophysiologic effects of flecainide acetate and its major metabolites in the canine heart. Am J Cardiol 1985 Mar 01;55(6):807-12

Date

03/01/1985

Pubmed ID

3919554

DOI

10.1016/0002-9149(85)90161-4

Scopus ID

2-s2.0-0021906706 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

Flecainide acetate, an investigational class 1 antiarrhythmic agent, undergoes biotransformation in man with production of 2 major metabolites: meta-O-dealkylated flecainide (S-24623) and the meta-O-dealkylated lactam of flecainide (S-26191). This study compared the effects of flecainide, S-24623 and S-26191 on cardiac electrophysiologic characteristics in the anesthetized dog. Each dog received 2 dose levels of 1 of the 3 test compounds after control measurements. Flecainide (2 and 4 mg/kg in 8 dogs), S-24623 (4 and 8 mg/kg in 8 dogs) and S-26191 (4 and 10 mg/kg in 7 dogs) were administered intravenously in dilute solution. Of the 3 compounds, only flecainide significantly prolonged sinus cycle length (p less than 0.01). However, both flecainide and S-24623 significantly prolonged minimum atrial paced cycle length with 1:1 atrioventricular conduction, atrioventricular nodal effective and functional refractory periods, and right ventricular effective refractory period. Metabolite S-26191 exhibited qualitatively similar but much weaker electrophysiologic actions. The maximal electrophysiologic effects of flecainide and S-24623 were approximately equivalent, but the metabolite was about one-half as potent on a milligram-permilligram basis, and lacked marked effects on infranodal (HV interval) conduction. S-26191 was less than one-tenth as potent as flecainide. Therefore, since both flecainide metabolites occur primarily in the conjugated form in plasma (i.e., free metabolite concentrations are low), it is unlikely that these compounds either potentiate flecainide's antiarrhythmic action or increase susceptibility to drug toxicity in the clinical setting.

Author List

Guehler J, Gornick CC, Tobler HG, Almquist A, Schmid JR, Benson DW Jr, Benditt DG

MESH terms used to index this publication - Major topics in bold

Animals
Anti-Arrhythmia Agents
Atrioventricular Node
Cardiac Pacing, Artificial
Dogs
Electrophysiology
Female
Flecainide
Heart
Heart Rate
Male
Piperidines
Sinoatrial Node
Time Factors
Ventricular Function