Suppression of resistant ventricular arrhythmias by twice daily dosing with flecainide

Duff, Henry J.; Roden, Dan M.; Maffucci, Rebecca J.; Vesper, Barbara S.; Conard, Gordon J.; Higgins, Stanley B.; Oates, John A.; Smith, Raymond A.; Woosley, Raymond L.

doi:10.1016/0002-9149(81)90331-3

Cited by 144 publications

(31 citation statements)

References 7 publications

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“…Flecainide acetate is a class Ic antiarrhythmic drug effective both in experimental and clinical ventricular and supraventricular tachyarrhythmias (Anderson et al, 1981;Duff et al, 1981;Campbell, 1983a;Hellestrand et al, 1984;Holmes & Heel, 1985;Somberg & Tepper, 1986). In cardiac muscle fibres, flecainide exhibits both very slow onset kinetics and recovery from V.ax block (Campbell & Vaughan Williams, 1983;Campbell, 1983a,b;Delpon et al, 1991) due to its high affinity for the activated and inactivated states of the Na channels (Anno & Hondeghem, 1990).…”

Section: Introductionmentioning

confidence: 99%

Effects of flecainide on isolated vascular smooth muscles of rat

Pérez‐Vizcaíno

Ding

Tamargo

1991

British J Pharmacology

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1 The inhibitory effects of flecainide were studied on contractile responses in rat isolated aortae and caudal artery and on spontaneous mechanical activity in portal vein segments.2 In rat isolated aorta flecainide, 1O-6m-5 x 10-0M, inhibited in a dose-dependent manner the contractile responses induced by high K (80mM) and noradrenaline (NA, 10-M). These inhibitory actions were observed when flecainide was added before or after the induced contractions and were similar in aortae with or without endothelium. 3 Contractile responses induced by addition of Ca to Ca-free high-K solution were also dosedependently inhibited by flecainide (IC50 = 2.5 + 0.3 x 10 -M). Moreover, flecainide inhibited the contractile responses elicited by NA in rings incubated in Ca-free solution.4 Flecainide also inhibited the spontaneous mechanical activity in portal vein segments (ICj0 = 6.5 + 0.9 x 1O 5M).5 Flecainide, 10-4M, inhibited 45Ca uptake stimulated by high K or NA without altering 45Ca uptake in resting aortae. 6 These results indicated that in rat isolated aortae, caudal arteries and portal veins, flecainide inhibited Ca entry through voltage-operated channels and NA-induced Ca uptake as well as Ca release from intracellular stores, thus decreasing the availability of intracellular free Ca required for vascular smooth muscle contraction.

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Section: Introductionmentioning

confidence: 99%

Effects of flecainide on isolated vascular smooth muscles of rat

Pérez‐Vizcaíno

Ding

Tamargo

1991

British J Pharmacology

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“…Flecainide acetate [2,5 bis (2,2,2-trifluoroeth-et al, 1981;Duff et al, 1981;Duran etal., 1982; oxy)-N-(2-piperidylmethyl) benzamide acetate; Hodges et al, 1982 flecainide and meta-O-dealkylated lactam of flecainide, which are recovered in urine both in the free and conjugated (glucuronide/sulphate) forms McQuinn et al, 1984). The present study was undertaken to evaluate the kinetics of flecainide in healthy volunteers after oral and intravenous administration, its absolute bioavailability, the influence of food intake and aluminium hydroxide on flecainide absorption and the accumulation and steadystate kinetics of flecainide during chronic oral treatment.…”

Section: Introductionmentioning

confidence: 99%

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

Tjandramaga¹,

Verbesselt²,

Hecken³

et al. 1986

Brit J Clinical Pharma

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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.

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“…It effectively antagonises atrial and ventricular arrhythmias in dogs induced by aconitine, ouabain, and coronary artery ligation after both oral and intravenous administration (Schmid et al, 1975). In man, preliminary reports indicate that the drug is effective for treating ventricular arrhythmias (Anderson et al, 1981;Duff et al, 1981;Gulker etal., 1981;Hellestrand etal., 1981a, b;Klempt etal., 1980;Seipel et al, 1981;Somani, 1980). Electrophysiological studies in dogs have shown that flecainide depresses conduction in all myocardial tissues, most notably in the His-Purkinje system and in ventricular muscle (Hodess et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

The haemodynamic effect of intravenous flecainide acetate in patients with coronary artery disease.

Serruys¹,

Vanhaleweyk²,

Brand³

et al. 1983

Brit J Clinical Pharma

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1 Flecainide acetate has been shown to be a potent antiarrhythmic agent which is active for more than 8 h, whether given intravenously or orally. However, the negative inotropic effect demonstrated in animal studies could hamper the potential clinical utility of the drug. 2 Ten patients with coronary artery disease but without cardiac failure were given intravenous flecainide (2 mg/kg). Stroke index (SI), left ventricular systolic pressure (LVP), end diastolic pressure (EDP) and LV contractility indices (max dP/dt, VCE 40 mm Hg, peak VCE, Vmax from total pressure (TP)) were measured immediately before and 10 min after flecainide, under resting conditions and during atrial pacing with heart rates up to 133 + 4.2 beats/min (mean + s.e. mean). 3 It is demonstrated that flecainide has a negative inotropic effect, not only under resting conditions, but also less apparently during pacing-induced tachycardia. The effect appears to be dose-related and may result in a reduction of cardiac performance.

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Suppression of resistant ventricular arrhythmias by twice daily dosing with flecainide

Cited by 144 publications

References 7 publications

Effects of flecainide on isolated vascular smooth muscles of rat

Effects of flecainide on isolated vascular smooth muscles of rat

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

The haemodynamic effect of intravenous flecainide acetate in patients with coronary artery disease.

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