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

Tjandramaga, T. B.; Verbesselt, René; Hecken, A. Van; Mullie, A.; Schepper, P. J. De

doi:10.1111/j.1365-2125.1986.tb02892.x

Cited by 35 publications

(19 citation statements)

References 11 publications

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“…This is thought to be caused by a conduction delay due to flecainide blocking the sodium channel in the cardiac muscle [17]. The prolongation rate of the QRS and QT intervals in the 3-mg/kg group substantially exceeded the rates for the other two groups.…”

Section: Discussionmentioning

confidence: 97%

Safe and Efficacious Dosage of Flecainide Acetate for Treating Equine Atrial Fibrillation.

Ohmura

Nukada

Mizuno

et al. 2000

The Journal of Veterinary Medical Science

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ABSTRACT. To determine a safe and efficacious dose of flecainide acetate for treating equine atrial fibrillation (Af), the safe dosage level was determined by injecting 1, 2, or 3 mg/kg i.v. of 1% flecainide acetate solution at a rate of 0.2 mg/kg/min to five clinically healthy horses. Clinical signs and the ECG were monitored (HR, PR, QRS, and QT intervals) and blood was taken to measure the plasma flecainide concentration pre-and post-administration. No abnormal signs were observed in the 1-or 2-mg/kg groups, while agitation was observed in three of five horses in the 3-mg/kg group. The QRS, and QT intervals for the 3-mg/kg group increased significantly. The peak plasma flecainide concentrations were 1,316 ± 358 (SD) ng/ml, 1,904 ± 314 ng/ml, and 2,251 ± 387 ng/ml for the 1-, 2-, and 3-mg/kg groups, respectively. To evaluate the efficacy of flecainide, Af was induced by right atrial pacing in six clinically healthy horses, and 1% flecainide acetate solution was then administered until they converted to sinus rhythm. All horses with induced Af converted. For the conversion, a total dose of 1.40 ± 0.63 mg/kg flecainide was required, the duration of administration was 7.00 ± 3.15 min and plasma flecainide concentration at conversion was 1,303 ± 566 ng/ml. In conclusion, flecainide acetate is a safe and effective antiarrhythmic agent for equine Af, and the clinically effective dosage is 1 to 2 mg/kg. Atrial fibrillation (Af) is one of the most common arrhythmias encountered in horses. It is thought that treatment is necessary for Af that does not recover spontaneously [1,4]. There have been a number of reports on Af in horses. Most of these studies used quinidine for treatment [1,11,14]. However, quinidine is known to have a number of side effects, including nasal mucosal edema, dyspnea, diarrhea, colic, tachycardia and laminitis [6,9]. Successful treatment has not been reported using any drug other than quinidine [10]. It would be highly desirable to convert equine Af, using an antiarrhythmic agent with less severe side effects than quinidine.In humans, a wide variety of antiarrhythmic agents have been developed and clinically applied to Af. Flecainide is an antiarrhythmic agent of Vaughan-Williams class Ic, a different class than quinidine [7]. In humans, flecainide has been shown to be effective in treating both supraventricular and ventricular arrhythmias. The rate of cardioversion of paroxysmal Af exceeds 90%, which is higher than that for other antiarrhythmic agents [2,8]. With side effects seldom involving organs other than the heart, flecainide is a relatively safe drug [5]. Nonetheless, flecainide has not been tried in horses, nor has its ability to convert equine Af been evaluated.In this study, we examined the safety and effectiveness of flecainide acetate in treating induced Af in horses. The efficacious dosage and rate of administration of flecainide was determined using clinical observations, ECG, and measurement plasma flecainide concentrations as indicators of side effects. MATERIALS AND METHODSStu...

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Section: Discussionmentioning

confidence: 97%

Safe and Efficacious Dosage of Flecainide Acetate for Treating Equine Atrial Fibrillation.

Ohmura

Nukada

Mizuno

et al. 2000

The Journal of Veterinary Medical Science

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“…The pharmacokinetic parameters in individual patients were estimated by the Bayesian method using a post‐hoc option of the NONMEM program. The time required to reach the peak concentration after oral administration of a conventional preparation of flecainide is short (mean ± SD: 2.3 ± 0.7 h) . In the present study, no plasma concentration data of flecainide were obtained in the absorption phase (0–2.5 h after oral administration).…”

Section: Methodsmentioning

confidence: 60%

Pharmacokinetic variability of flecainide in younger Japanese patients and mechanisms for renal excretion and intestinal absorption

Horie

Ishida

Shibata

et al. 2013

Biopharm & Drug Disp

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The aims of the present study were to evaluate the variability of pharmacokinetics of flecainide in young Japanese patients and to investigate the mechanisms of renal excretion and intestinal absorption of the drug using cultured epithelial cells. First the plasma concentration data of flecainide was analysed in 16 Japanese patients aged between 0.07 and 18.30 years using a one-compartment model. Considerable interindividual variability was observed in the oral clearance (CL/F) and the apparent volume of distribution (V/F) of flecainide in the young patients. Flecainide was transported selectively in the basolateral-to-apical direction in P-glycoprotein-expressing renal epithelial LLC-GA5-COL150 cell monolayers. The uptake of flecainide into intestinal epithelial LS180 cells was decreased significantly by acidification of the extracellular medium, and was inhibited by tertiary amines, such as diphenhydramine and quinidine. These findings in the present study suggest that flecainide is excreted by P-glycoprotein in the renal tubule and is taken up by the postulated H(+)/tertiary amine antiporter in the intestine, and that functional variability of not only the hepatic drug-metabolizing enzymes, but also the transporters in the kidney and intestine, may be responsible for the interindividual variability of systemic clearance (CL) and/or the bioavailability (F) of flecainide.

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“…Although several studies have been published recently on the pharmacokinetics of FLC (4)(5)(6)(7), particularly in patients with reduced renal function (8,9), very few data are available about its pharmacokinetics in critically ill patients.…”

Section: Introductionmentioning

confidence: 99%

Clinical Pharmacokinetics of Intravenous Flecainide in Critically Ill Patients

et al. 1989

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Plasma flecainide (FLC) levels versus time were measured in a group of 10 acute myocardial infarction (AMI) patients at our Intensive Care Unit. These patients were treated with single doses of 150 mg FLC as a 30-min intravenous infusion. Mean FLC plasma concentration values at 0, 1, 2, 4, and 8 h following administration were 562 +/- 271, 342 +/- 129, 270 +/- 90m, 240 +/- 80 and 210 +/- 60 ng/ml, respectively. Flecainide pharmacokinetics fitted an open two-compartment model, with a rapid distribution phase and a slow elimination phase. Mean values for the terminal plasma half-life (t1/2 beta) was 22.0 +/- 9.7 h and the volume of distribution (V beta) was 7.99 +/- 3.02 1/kg. FLC is different to other i.v. antiarrhythmics in having a prolonged plasma half-life which is a decided advantage. In contrast to lidocaine, FLC has a pharmacokinetic profile that enables it to be used for treating ventricular arrhythmia without constant-rate i.v. infusion and without the need for complicated loading dosages in order to avoid a 'pharmacokinetic dip' over the first hour of treatment.

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

Cited by 35 publications

References 11 publications

Safe and Efficacious Dosage of Flecainide Acetate for Treating Equine Atrial Fibrillation.

Safe and Efficacious Dosage of Flecainide Acetate for Treating Equine Atrial Fibrillation.

Pharmacokinetic variability of flecainide in younger Japanese patients and mechanisms for renal excretion and intestinal absorption

Clinical Pharmacokinetics of Intravenous Flecainide in Critically Ill Patients

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