A controlled trial of propafenone for treatment of frequent and repetitive ventricular premature complexes

Salerno, David M.; Granrud, Gregory; Sharkey, Patricia; Asinger, Richard W.; Hodges, Morrison

doi:10.1016/0002-9149(84)90687-8

Cited by 131 publications

(29 citation statements)

References 17 publications

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“…This resulted in considerably higher serum concentrations of the metabolites despite comparable serum concentrations of the parent compound. Thus, the concentration-effect relationship in the same patient may differ after oral and intravenous doses if concentrations of the active metabolite(s) are not taken into consideration.Although the mechanism of the nonlinearity is not clear, the data indicate that it may be due to saturable biliary excretion of the metabolites.Key words: Propafenone; metabolism, nonqinear pharmacokinetics, 5-hydroxypropafenone, N-depropylpropafenone, saturable biliary excretion Propafenone is a relatively new Class Ic antiarrhythmic agent that has been shown to be effective in the treatment of ventricular and supraventricular arrhythmias [1][2][3]. The pharmacokinetics have investigated after single and multiple doses in healthy subjects [4] and in patients in steady-state on oral therapy [5].…”

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confidence: 99%

Nonlinear kinetics of propafenone metabolites in healthy man

Haefeli

Vlcek

et al. 1990

Eur J Clin Pharmacol

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The pharmacokinetics of oral and i.v. propafenone and its major metabolites have been investigated in 8 healthy subjects. The total body clearance of propafenone was 963 ml/min, the terminal half-life 198 min and its absolute bioavailability was 15.5%. The two active metabolites (5-hydroxypropafenone and N-depropylpropafenone) showed non-linear kinetics in that both the dose-corrected area under the serum concentration-time curve and the amount excreted in the urine were larger after oral dosing. This resulted in considerably higher serum concentrations of the metabolites despite comparable serum concentrations of the parent compound. Thus, the concentration-effect relationship in the same patient may differ after oral and intravenous doses if concentrations of the active metabolite(s) are not taken into consideration. Although the mechanism of the nonlinearity is not clear, the data indicate that it may be due to saturable biliary excretion of the metabolites.

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confidence: 99%

Nonlinear kinetics of propafenone metabolites in healthy man

Haefeli

Vlcek

et al. 1990

Eur J Clin Pharmacol

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“…Propafenone is known to reduce LV systolic performance in patients who have underlying LV dysfunction [27][28][29], as assessed by systolic time intervals and by two dimensional echocardlography. However, the data are inadequate to make a definitive statement regarding the effects of proprafenone on myocardial contractility.…”

Section: Dipra[enone's Cardiodepressive Propertiesmentioning

confidence: 99%

Influence of the new class I antiarrhythmic agent diprafenone on the end-systolic pressure-volume relationship (conductance technique)

Thormann

Krämer

Kremer

et al. 1989

Cardiovasc Drug Ther

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To evaluate cordiodepressive risks of antiarrhythmic treatment with diprafenone, we monitored, in addition to conventional hemodynamic parameters, end-systolic pressure-volume relations to assess potential negative inotropic effects. Thirteen patients underwent hemodynamic analysis with and without the influence of diprafenone 1.5 mg/kg, both a) at rest (paced heart rate of 90 beats/min and b) during tachycardia (paced tachycardia of 160 beats/min). Left ventricular volumes increased under the influence of diprafenone, both at rest (end-diastolic volume by an average of 12%, end-systolic volume by 21%) and during tachycardia (by 15% and by 47%, respectively). Diprafenone induced a depression of left ventricular function during tachycardia only: Ejection fraction fell by an average of 25% and stroke work by 19%, while end-diastolic pressure increased by an average of 28% and systemic vascular resistance by 34%. Diprafenone caused the loops of the end-systolic pressure-volume relationship to move rightward and decreased the slope k, indicating negative entropy, both at rest and during tachycardia. Thus, since under the influence of diprafenone negative inotropic effects and depressed left ventricular function were found (while determinants of preload and afterload increased), diprafenone should not be used as an antiarrhythmic agent in patients with advanced cardiac failure.

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“…Propafenone resulted in a modest but significant prolongation of the AV nodal conduction time (AH interval control 54 k 7 ms; 63 +-7 ms post last dose). 3). AV nodal effective and functional refractory periods could be measured in seven of the puppies.…”

Section: Heart Rate and Bloodpressure (Table Imentioning

confidence: 99%

The Electrophysiologic Effects of Propafenone Hydrochloride in the Neonatal Canine

Villafañe

Gelband

et al. 1987

Pediatr Res

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ABSTRACT. The electrophysiologic effects of the new antiarrhythmic agent, propafenone, were investigated in 10 mongrel canine neonates, ages 5 to 11 days. Utilizing standard His bundle recording and stimulation techniaues. assessments of sinus and atrGventricular (AV) node func: tion and atrial, AV nodal, and ventricular refractory periods were performed prior to (control) and after cumulative intravenous doses of 1, 2, and 4 mg/kg of propafenone. Provafenone depressed the svontaneous heart rate and the postatrial pacing recovery times. AV nodal function was de~ressed as manifested bv Wenckebach periodicity occurring at slower pacing rates, increases in AV nodal conduction time, and increases in AV nodal refractoriness. Atrial and ventricular refractory periods were prolonged significantly in a dose-dependent fashion. arrhythmias. Furthermore, the electrophysiologic effects of type IC agents in general have not been defined in the immature heart. Current information available concerning the effects of propafenone have been derived from studies of isolated cardiac tissues (9, 10) and studies in adult humans (2, 6, 11) and adult dogs (12). We undertook this study to assess the electrophysiologic responses of the immature mammalian heart to incremental doses of this new antiarrhythmic agent. METHODSTen mongrel canine neonates, ages 5 to 11 days, were studied. All animals were anesthetized with sodium pentobarbital, 30 mg/kg intraperitoneally, and supplemented intravenously as needed to maintain anesthesia. The dogs were mechanically ventilated with a Hamard respirator.Surface electrocardiographic lead I1 and femoral artery blood pressure were constantly monitored. Three electrode catheters were used for intracardiac electrogram recordings and stimulation and were positioned utilizing fluoroscopic visual guidance. A no. 5 French quadripolar catheter was positioned in the high right atrium using a right femoral vein approach; a no. 5 French quadripolar catheter was positioned in the right ventricular apex using a right jugular vein approach and, in brder to record the His bundle electrogram, a no. 4 French tripolar catheter was positioned in the noncoronary aortic cusp via the left carotid artery. Intracardiac electrograms were amplified at a filter setting of 40-500 Hz and displayed with the surface ECG on a multichannel oscilloscope (Electronics for Medicine, DR-6). Recordings were made on direct writing paper (Kodak Linagraph Paper 220 1) at a vaver sveed of 100 mmls.~Aificiai siimuiation was perfokned utilizing a programable digital stimulator (Medtronics, model 5325). Electrical impulses of 2 ms duration were delivered at twice diastolic threshold. Atrial and ventricular single extrastimulation was performed by introducing a premature beat (S2) after every eighth paced beat of a paced cycle length (SISI) at 10 ms decrements until atrial or ventricular refractoriness was reached. Rapid atrial and ventricular pacing for 30 and 15 s, respectively, was performed starting at a rate slightly above the resting heart ra...

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A controlled trial of propafenone for treatment of frequent and repetitive ventricular premature complexes

Cited by 131 publications

References 17 publications

Nonlinear kinetics of propafenone metabolites in healthy man

Nonlinear kinetics of propafenone metabolites in healthy man

Influence of the new class I antiarrhythmic agent diprafenone on the end-systolic pressure-volume relationship (conductance technique)

The Electrophysiologic Effects of Propafenone Hydrochloride in the Neonatal Canine

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