Pharmacokinetics and electrocardiographic effects of a new controlled‐release form of flecainide acetate: Comparison with the standard form and influence of the CYP2D6 polymorphism

Abstract

Flecainide-induced QRS prolongation did not differ between the new controlled-release form and the immediate-release form. Flecainide plasma concentrations associated with the new controlled-release form predicted QRS prolongation with less variability compared with the immediate-release form. The CYP2D6 polymorphism did not appear to influence flecainide disposition kinetics or electrocardiographic effects at steady state.

Effects of CYP2D6*10, CYP3A5*3, CYP1A2*1F, and ABCB1 C3435T polymorphisms on the pharmacokinetics of flecainide in healthy Chinese subjects

“…The study results suggested that CYP3A5 and CYP1A2 might play a role in the disposition of fl ecainide, in particular in carriers of less active forms of CYP2D6. The lack of signifi cant association between the CYP2D6*10 polymorphism and the pharmacokinetics of fl ecainide observed in the study is consistent with the fi ndings from some previous studies with repeated doses of fl ecainide in healthy subjects phenotyped as CYP2D6 extensive metabolizers (EMs) and PMs (9,10) , although an early study in 10 Caucasian subjects (n = 10, including 3 females) showed that CYP2D6 PMs (n = 5), determined by sparteine-debrisoquin phenotype, had a 42 % reduction in fl ecainide clearance and 70 % increase in AUC 0-∞ compared to EMs after a single dose of 50 mg (8) .…”

“…CYP2D6 polymorphisms have been shown, but not always (9,10) , to signifi cantly infl uence the pharmacokinetics of fl ecainide in healthy subjects (11) and in patients with supraventricular tachyarrhythmia (6) . Although CYP2D6 is considered to play a predominant role in the metabolism of fl ecainide, considerable MODF and MODLF can be detected in CYP2D6 poor metabolizers (PMs) (8,12) .…”

Impact of the control of symptomatic paroxysmal atrial fibrillation on health-related quality of life

“…The first is an immediate-release formulation (Flec IR) to be taken twice a day, the second is a once-a-day controlled-release formulation (Flec CR). 26 …”

Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

“…Quinidine has only a slight effect on flecainide concentrations (Birgersdotter et al, 1992). CYP2D6 status does not seem to predict electrophysiological effects in volunteers (FunckBrentano et al, 1994;Tenneze et al, 2002). Overall, the gene-concentration and gene-effect relationships between CYP2D6 and flecainide seem minor, at least in healthy subjects, and the other pathways of elimination would make significant effects unlikely.…”

“…Flecainide is inactivated by mechanisms that include metabolism by CYP2D6 (Mikus et al, 1989;Gross et al, 1991) and renal elimination that is pH-dependent (Funck-Brentano et al, 1994). PMs have 2-fold higher mean flecainide concentrations than EMs after single doses (Mikus et al, 1989;Gross et al, 1991), but a negligible difference at steady state (Funck-Brentano et al, 1994;Tenneze et al, 2002). Quinidine has only a slight effect on flecainide concentrations (Birgersdotter et al, 1992).…”