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PubMed1986

Oxidative metabolism of encainide: polymorphism, pharmacokinetics and clinical considerations.

The 8-h urinary metabolic profiles of encainide and its oxidized metabolites, O-desmethyl- (ODE), 3-methoxy-O-desmethyl- (MODE), N-desmethyl- (NDE) and N, O-didesmethyl- (DDE) encainide were studied in a group of 112 normal Caucasians. Nine of these subjects (8%) were defective in their ability to 4-hydroxylate debrisoquine. The cumulative frequency distribution of the 8-h recovery ratio of encainide/ODE indicated two distinct populations in complete concordance with the debrisoquine phenotyping. The subjects with an 'extensive metabolizer' (EM) phenotype had a ratio from 0.003 to 0.9 whereas the PM group had values from 7.4 to 48. In addition, no MODE was detected in the urine from 'poor metabolizers' (PM). The oxidative metabolism of encainide, specifically the O-demethylation pathway, is, therefore, polymorphically distributed and controlled by the same genetic factor(s) that determine the 4-hydroxylation of debrisoquine. In EM subjects, ODE and MODE are the major metabolites in plasma and their concentrations are much greater than those of unchanged drug. As ODE is a more potent antiarrhythmic agent than encainide and MODE is at least equipotent, these metabolites significantly contribute to the overall antiarrhythmic effect in EM patients. The low plasma concentrations of ODE and MODE in PM subjects would be expected to result in inefficacious therapy when usual doses of encainide are administered. However, in such individuals, chronic oral therapy results in accumulation of unmetabolized encainide to far higher levels than in EM subjects. As encainide itself has intrinsic antiarrhythmic activity at these concentrations, this generally results in the desired clinical response. Despite pronounced interphenotypic differences in encainide's disposition and pharmacokinetics, the polymorphic oxidative metabolism appears to have limited consequences for the drug's clinical efficacy.

Adolescent↗
PubMed1985

[Acute and long-term antiarrhythmia effect of encainide in chronic atrial extrasystole].

The antiarrhythmic effects of Encainide in acute intravenous and long-term oral therapy were investigated in 10 patients suffering from chronic atrial ectopic beats previously non-responsive to conventional therapy. The efficacy of Encainide was assessed by 24-hour ECG monitoring during the acute i.v. application and in 4 week intervals over a period of 4 to 6 months. Plasma concentrations of Encainide and the O-demethyl- (ODE) and 3-methoxy-O-demethyl metabolites (3-MODE) were determined after i.v. administration and during oral therapy. A significant reduction of arrhythmias by 76% was found after 1.0 mg/kg Encainide given intravenously. Atrial ectopic beats with bundle branch block QRS-morphology were reduced by more than 90% after only 0.5 mg/kg. During long-term oral therapy 6 of the 9 patients were treated successfully. Following i.v. administration Encainide-plasma concentrations rapidly decreased with a half life of approximately 75 min in the final distribution phase. During oral therapy Encainide levels were not detectable under steady state conditions 4 to 6 hours after the last dose, or they were only minimal, but the average concentrations of ODE and 3-MODE were 71.3 +/- 21.3 and 75.6 +/- 13.5 ng/ml. Encainide increased PR interval and QRS duration significantly. QT-interval changed as a result of the QRS-prolongation. Encainide was well tolerated during acute and chronic therapy. No severe side effects were seen, except in one case, in which dose reduction by 50% was necessary because of blurred vision.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Reevaluation of digoxin-encainide interactions using an animal model.

The effects of intravenous encainide on digoxin-induced atrial ectopic tachycardia (AET) were investigated in the rat using 3-channel simultaneous limb-lead electrocardiography. Pentobarbital-anesthetized (35 mg/kg, intraperitoneal) adult male rats were given digoxin subcutaneously, 30 mg/kg. After onset of AET, rats received either saline (0.5 ml/kg) or encainide; 0.25, 0.5, 1.0, or 2.0 mg/kg intravenously in repeated doses at 15-min intervals. At all doses, encainide converted digoxin-induced AET to ventricular arrhythmias, prolonged recovery time, and increased mortality in comparison to saline-treated animals. An additional group of anesthetized rats was not given digoxin. These animals received encainide (2.0 mg/kg, intravenously) in repeated doses at 15-min interval and developed dose-related increase in the P-R interval only. Blood samples were obtained by cardiac puncture from 12 additional anesthetized, digoxin-treated rats 5 min after the fourth intravenous dose of saline (0.5 ml/kg, n = 6) or encainide (1.0 mg/kg, n = 6). Serum was prepared and analyzed by affinity column-mediated immunoassay. Digoxin levels were the same in both groups. These results suggest that encainide may exacerbate digoxin-induced arrhythmias (proarrhythmic effect) in this species. In view of our findings of digoxin-encainide interactions in the rat, we recommend caution if these drugs are coadministered in humans.

Anilides↗
PubMed1990

Encainide versus flecainide in the treatment of chronic resistant paroxysmal atrial tachyarrhythmias.

To determine the relative safety and efficacy of oral encainide, ten patients with a long (mean 10 years) history of resistant paroxysmal atrial tachyarrhythmias that were finally controlled with flecainide were selected. All patients were resistant to previously used Class 1A antiarrhythmic drugs, and amiodarone was ineffective or insufficient in eight. Flecainide (mean 200 mg/day) given alone in five patients, or combined with amiodarone in four, and nadolol in one had been used for a mean of 19 months (range, 4-48). The clinical efficacy was considered good in five patients and fair in five, and tolerance was good in four, fair in three, and poor in three. Flecainide was replaced with encainide (153 mg/day; range, 50-225 mg/day) for a mean duration of 6.2 months (range, 0.5-14.2 months). Encainide was effective in five patients, partly effective in two, and ineffective in three. Tolerance was good, except for vertigo reported by two patients. Flecainide was clearly or slightly more effective than encainide in five patients, equally as effective as encainide in three, and less effective than encainide in two. Tolerance of encainide was better than flecainide in six patients, equal to flecainide in two, and worse in two. The results of the present study may be biased because the patients were selected on the basis of flecainide efficacy and tolerance. However, the results reflect the equivalence of the two drugs in clinical practice for the treatment of particularly resistant arrhythmias.

Adult↗
PubMed1991

Effect of encainide, ODE, MODE, and flecainide on ADP/5-HT induced platelet aggregation and in the anesthetized dog coronary artery stenosis-occlusion model of intravascular thrombosis.

Encainide is a class 1C antiarrhythmic agent that is indicated for the treatment of life-threatening arrhythmias, such as sustained ventricular tachycardia. Furthermore, encainide possesses a moderate degree of antiserotonin activity, which was quantitated in this present study by determining displacement of [3H]spiperone binding from rat cortical 5-HT2 binding sites. The Ki for encainide in this model was 66.1 nM, compared to 2.6 nM for ketanserin. Two encainide metabolites, ODE and MODE, were also active, but were weaker than encainide. Additionally, these agents were found to inhibit platelet aggregation induced in vitro in human platelet-rich plasma by the combination of ADP and serotonin. In view of the fact that serotonin is one of a variety of humoral factors capable of activating blood platelets and has been recently implicated as playing a role in certain thrombotic syndromes, encainide, along with its two principal human metabolites, ODE and MODE, and another class 1C antiarrhythmic, flecainide, were evaluated in an in vivo model of intravascular thrombosis. Intraduodenal doses of 1 mg/kg of either encainide, ODE, or MODE significantly inhibited thrombosis in a canine model of coronary artery stenosis-occlusion.

Adenosine Diphosphate↗
PubMed1984

Differential effects of O-demethyl encainide on induced and spontaneous arrhythmias in the conscious dog.

Encainide is highly effective in suppressing most nonsustained ventricular arrhythmias, but there is evidence that the drug is less effective and may worsen some arrhythmias, particularly in patients with sustained ventricular tachycardia. In most patients it is likely that the major antiarrhythmic effects of encainide are mediated through a potent metabolite, O-demethyl encainide. The effects of infusions of saline solution or O-demethyl encainide on spontaneous ventricular ectopic activity and ventricular fibrillation (VF) threshold were compared in 25 dogs with a mottled myocardial infarct produced by transient coronary occlusion. Plasma levels of the metabolite above 100 ng/ml suppressed (greater than 92%) the spontaneous ventricular ectopic activity that occurred 48 hours after MI, whereas saline solution had no effect. In 15 dogs treated with O-demethyl encainide, the VF threshold decreased an average of 23%, from a baseline level of 23 +/- 8 mA to 18 +/- 9 mA (p less than 0.05). There was a concentration-dependent fall in VF threshold with plasma concentrations of O-demethyl encainide above 150 ng/ml. In 2 dogs with very high plasma concentrations of the metabolite (greater than 1,000 ng/ml), VF was induced by right ventricular pacing alone (S1S1 300 ms). No change in VF threshold was observed in the 8 dogs treated with saline solution, and in each of these dogs VF could be terminated by the countershock protocol. However, in 7 of the 17 dogs treated with O-demethyl encainide, VF could not be terminated by the countershock protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗
PubMed1986

Electrophysiology in assessing supraventricular arrhythmias: value of programmed stimulation in predicting and understanding efficacy of encainide.

The effects of intravenous (1.5 mg/kg body weight given over 15 minutes) and oral (mean dose 164.8 +/- 56.2 mg/day) encainide were studied in 11 patients with recurrent, difficult to treat, supraventricular tachycardia. In 2 patients the arrhythmia was atrial in origin. In 9 patients a concealed (slow type in 3, fast type in 6) accessory atrioventricular pathway was used for retrograde conduction during a circus movement tachycardia. Intravenous encainide terminated tachycardia in 8 of the 11 patients. Oral encainide prevented clinical recurrence of tachycardia in 7 patients during a 5- to 20-month follow-up (mean 11). Programmed stimulation of the heart after intravenous encainide administration revealed significant (p less than 0.05) prolongation of HV interval, QRS width and refractory period of the right ventricle. Apart from a slower tachycardia rate no changes in electrophysiologic parameters were observed in 5 patients restudied while receiving oral encainide medication. Although encainide was an effective antiarrhythmic agent, programmed stimulation of the heart was not very helpful in providing insight into its mode of action, nor did programmed stimulation predict clinical efficacy. Prevention of the tachycardia-initiating premature beat seems to be the most likely mechanism for the clinical efficacy of oral encainide.

Administration, Oral↗
PubMed1986

Encainide for treatment of supraventricular tachycardias associated with the Wolff-Parkinson-White syndrome.

Thirty-three patients with supraventricular tachycardia associated with the Wolff-Parkinson-White syndrome were treated with encainide for 26 months (mean). Encainide at a mean dosage of 187 mg/day abolished or markedly decreased episodes of palpitations in 24 of 33 (73%), and no patient had syncope or required cardioversion while receiving the drug. Encainide was well tolerated and was discontinued in only 2 patients because of side effects (6%). Only 1 patient (3%) had a proarrhythmic effect while taking encainide (ventricular tachycardia). Fourteen of 16 patients (88%) with atrial fibrillation continue receiving encainide. Episodes of palpitations have been abolished or markedly decreased and no patient has had syncope or required cardioversion. All 14 of these patients had either anterograde block in the accessory pathway during atrial fibrillation or greater than or equal to 75 ms increase in the shortest R to R interval formed by 2 preexcited QRS complexes. Encainide prolonged refractory periods of the atrial (p = 0.064) and ventricular (p = 0.061) muscle. It prolonged the cycle length at which 1:1 conduction of the accessory pathway in both the anterograde and retrograde directions occurred (both, p less than 0.001). Induction of atrioventricular-reciprocating tachycardia (AVRT) was prevented in 36% of patients at repeat electrophysiologic study. The AVRT cycle length increased 112 ms (mean, p less than 0.001) in those patients in whom AVRT was still inducible. The loss of delta waves recorded with the 12-lead scalar electrocardiogram during encainide therapy was a significant predictor of anterograde accessory pathway block (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Relation of blood level and metabolites to the antiarrhythmic effectiveness of encainide.

Encainide is a potent new antiarrhythmic agent with 2 major active metabolites and 2 distinct phenotypes for metabolism, extensive (approximately 92%) and nonextensive (8%). Encainide is an active compound with close correlation of plasma levels with antiarrhythmic effectiveness and electrocardiographic changes in nonextensive metabolizers. Its metabolites, O-demethyl-encainide and 3-methoxy-O-demethyl-encainide, are active against experimental and clinical arrhythmias. They have longer half-lives than and equal or greater potency than the parent compound. All 3 compounds contribute to the antiarrhythmic profile in extensive metabolizers. There is no readily apparent relation between encainide and its metabolites, blood levels and efficacy because of the complexity of the 3 active compounds and individual variation in pharmacokinetic and arrhythmia responsiveness. Encainide has been given for up to 2 years in 140 patients with sustained ventricular tachycardia or ventricular fibrillation. The survival curves are similar to historical control data from patients reported by Graboys and Swerdlow. The survival curves for long-term administration in patients with frequent ventricular premature complexes (greater than 30/min) are comparable to data from Califf. While these data must be viewed cautiously, it seems fair to conclude that encainide is as effective as any combination of drugs for preventing sudden death in patients with life-threatening ventricular arrhythmias.

Anilides↗
PubMed1988

Encainide for treatment of atrioventricular reciprocating tachycardia in the Wolff-Parkinson-White syndrome.

Oral encainide, varying from 75 to 300 mg/day (mean 174 mg/day), was administered to 52 patients with drug-resistant atrioventricular reciprocating tachycardia (AVRT) associated with the Wolff-Parkinson-White syndrome. Electrophysiologic studies were performed before and during drug treatment. Encainide resulted in anterograde accessory pathway block in 15 of 37 (41%) and retrograde accessory pathway block in 11 of 46 (24%) patients. In patients with residual accessory pathway conduction, encainide significantly prolonged the shortest pacing cycle length maintaining anterograde (261 +/- 26 to 404 +/- 85 ms) and retrograde (279 +/- 46 to 436 +/- 87 ms) accessory pathway conduction, as well as the anterograde accessory pathway effective refractory period (271 +/- 32 to 329 +/- 73 ms). AVRT could not be induced during encainide therapy in 20 of 49 patients (41%). In the remaining patients, AVRT cycle length increased (319 +/- 44 to 426 +/- 90 ms, p less than 0.001) due to prolongation of HV and ventriculoatrial intervals. During follow-up (mean 38.5 months), 30 patients continued to take the drug and 7 patients with favorable drug response subsequently elected to undergo surgical accessory pathway ablation (71% overall favorable response). Encainide was ineffective in 11 patients, was discontinued because of drug intolerance in 2 patients and exacerbated ventricular tachycardia in 2 patients. Lack of AVRT inducibility at encainide electrophysiologic study did not always predict recurrence-free follow-up. Encainide is an effective and well-tolerated drug to prevent recurrence of AVRT in patients with Wolff-Parkinson-White syndrome.

Administration, Oral↗
PubMed1988

Encainide for atrial fibrillation associated with Wolff-Parkinson-White syndrome.

Thirty-six patients with a history of atrial fibrillation and Wolff-Parkinson-White syndrome were treated with oral encainide, 175 +/- 44 mg/day, after undergoing baseline drug-free electrophysiologic studies. The mean age was 38 +/- 15 years, with structural heart disease present in only 3 patients. Nine patients had only paroxysmal atrial fibrillation and 27 patients had both atrial fibrillation and atrioventricular reciprocating tachycardia (AVRT). Symptoms were present for a mean of 195 +/- 168 months and were treated with an average of 2.7 +/- 1.6 drugs before encainide. Anterograde block in the accessory pathway occurred in 12 of 30 patients (40%) and retrograde block accessory pathway occurred in 10 of 24 patients in whom comparison could be made. AVRT was initiated in 29 of 36 patients during the control study and could be initiated in 19 of 29 patients while receiving encainide. Drug efficacy was determined by the clinical response judged completely effective, partially effective or ineffective. During a mean follow-up of 30.1 +/- 25 months, 24 patients (67%) continued to take encainide. Encainide was completely effective in 14 of 24 patients and partially effective in another 7 patients. Noncardiac side effects were mild and generally resolved, and required discontinuance in only 1 patient. More frequent AVRT occurred in 2 patients, but was managed with dose reduction and the addition of a beta blocker. Three patients had ventricular tachycardia requiring discontinuance; however 2 of 3 patients had a history of ventricular tachycardia before receiving encainide. Encainide is an effective and safe agent for treating atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

Adolescent↗
PubMed1990

Electrophysiologic and electrocardiographic effects, efficacy and safety of encainide in malignant ventricular arrhythmias associated with coronary artery disease.

The electrophysiologic and electrocardiographic effects, efficacy and safety of encainide were evaluated in 48 patients with coronary artery disease undergoing programmed stimulation for ventricular tachyarrhythmias. The study group included 41 men and 7 women, aged 64 +/- 8 years (mean +/- standard deviation), who had presented with nonsustained ventricular tachycardia (VT) (4 patients), sustained VT (32), ventricular fibrillation (8) or unexplained syncope (4). The left ventricular ejection fraction averaged 34 +/- 13%. The arrhythmias induced at the baseline, drug-free electrophysiologic study included nonsustained VT in 8 patients, sustained VT in 35 and ventricular fibrillation in 5. All patients had failed greater than or equal to 1 class IA and a combination of class IA and IB agents (mean 2.2 +/- 1.1 drugs) before encainide. Oral encainide was given in a mean daily dose of 80 +/- 11 mg for greater than or equal to 3 days before repeat programmed stimulation. Encainide was discontinued before follow-up electrophysiologic testing in 5 patients due to spontaneous development of new sustained VT. Of the 43 patients undergoing electropharmacologic testing with encainide, 5 had no inducible arrhythmia. In 9 patients VT was inducible by fewer extrastimuli, in 2 patients a previously stable VT required cardioversion, whereas in 28 patients VT remained inducible by the same number of or more extrastimuli. Thus, encainide prevented the induction of VT or ventricular fibrillation in 5 of 48 patients (10%), while it had a possible proarrhythmic effect in 15 patients (31%). Of the 5 patients without inducible VT administered long-term encainide therapy, 1 returned within 4 weeks of hospital discharge with VT recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1980

Electrophysiological effects of encainide on isolated cardiac muscle and Purkinje fibers and on the Langendorff-perfused guinea-pig heart.

The effect of encainide (0.1, 0.3 and 1.0 mg/l) on transmembrane electrical activity was studied in left auricle and papillary muscles of the guinea pig and in Purkinje fibers of cow and sheep hearts. Conduction times and refractoriness of the AV node and the His-Purkinje system were measured in the Langendorff-perfused guinea-pig heart by His-bundle recording. Encainide had no effect on the maximum diastolic potential. Action potential duration (100% repolarization) remained constant or slightly prolonged in guinea-pig auricle and ventricle preparations but was shortened in cow and sheep Purkinje fibers. Action potential amplitude and Vmax decreased in a dose-dependent manner, the effect being more pronounced at higher frequencies. The frequency effect was not related to a change in the recovery of Vmax following the repolarization. The drug reduced Vmax at all membrane potential values, the relative effect being slightly more pronounced at low membrane potentials. In three different tests for pacemaker activity encainide had no effect on the rate of diastolic depolarization at high levels of membrane potential, but clearly reduced the spontaneous oscillations at the plateau level and the transient depolarizations characteristic for triggered pacemaker activity induced by ouabain. Ca-mediated action potentials were not affected even at concentrations of encainide up to 8 mg/l. In the Langendorff-perfused guinea-pig heart, conduction through the His-Purkinje system was slowly more than conduction through the AV node. All effects were quickly reversible by drug-free perfusion. In comparison with lidocaine, the effect of encainide on electrical parameters showed the following differences: the decrease in Vmax in the presence of encainide was more frequency-dependent, and less potential-dependent, the effect of encainide on pacemaker activity was more selective.

Action Potentials↗
PubMed1989

Electrophysiologic and clinical effects of oral encainide in paroxysmal atrioventricular node reentrant tachycardia.

The electrophysiologic effects of oral encainide (75 to 150 mg daily) were evaluated in 14 patients (6 male and 8 female, aged 49 +/- 9 years) with atrioventricular (AV) node reentrant tachycardia of the slow-fast type. The patients were studied in control conditions and after 2 to 12 days of treatment. Encainide increased the AH interval from 67 +/- 10 to 82 +/- 23 ms (p less than 0.02). Anterograde Wenckebach cycle length was increased in three patients, reduced in four, unchanged in one; it was not measurable in the remaining patients because tachycardia was induced. Retrograde Wenckebach periodicity increased from 307 +/- 71 to 401 +/- 92 ms (p less than 0.005) in all nine patients in whom it was measurable; complete retrograde block was observed in one patient. At the control study, tachycardia was induced in all patients, with a mean cycle length of 341 +/- 50 ms; after encainide, tachycardia was inducible in only 1 patient, with an increase in cycle length from 270 to 320 ms; in the other patients, tachycardia was not inducible because of a lack of retrograde (11 patients) or anterograde (2 patients) conduction. The mean plasma concentrations of encainide and its metabolites O-demethyl-encainide and 3-methoxy-O-demethyl-encainide measured in 13 patients during the repeat study were 161 +/- 304, 128 +/- 100 and 95 +/- 85 ng/ml, respectively; three poor metabolizers who presented a high concentration of the parent compound were observed in this series. All patients were discharged on encainide at a mean daily dose of 112 +/- 39 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Suppression of incessant supraventricular tachycardia by intravenous and oral encainide.

Although uncommon, incessant supraventricular tachycardia (the daily presence of supraventricular tachycardia for more than 50% of the day) is a major therapeutic problem. Using programmed electrical stimulation of the heart, long-term electrocardiographic monitoring and exercise testing, the effect of intravenous and oral encainide for termination and prevention of incessant supraventricular tachycardia was assessed in 11 patients (aged 25 to 58 years). All patients had received 3 to 12 drugs (mean 6) without control of their arrhythmia. Eight patients suffered from incessant supraventricular tachycardia using an accessory pathway in retrograde direction (three with overt Wolff-Parkinson-White syndrome, one with a concealed accessory atrioventricular [AV] pathway of the fast type, three with a concealed accessory AV pathway of the slow type and one with a nodo-ventricular accessory pathway). Three patients had incessant atrial tachycardia, one of whom also had the Wolff-Parkinson-White syndrome. Intravenous encainide (1.5 mg/kg in 15 minutes) terminated incessant supraventricular tachycardia in seven of nine patients. In four of nine patients, supraventricular tachycardia could thereafter still be reinitiated by pacing. Oral encainide (100 to 325 mg/day, mean 180) completely suppressed the incessant supraventricular tachycardia in eight patients in a follow-up period of 5 to 20 months (mean 11). In two patients, episodes of tachycardia were markedly reduced with the administration of encainide in combination with sotalol (one patient) and amiodarone (one patient). Encainide failed to control incessant tachycardia in one patient. Mild central nervous system side effects developed in two patients, but both could continue taking oral encainide. Encainide proved to be a very useful agent to control incessant supraventricular tachycardia resistant to other antiarrhythmic agents.

Administration, Oral↗
PubMed1985

Comparative study of encainide and disopyramide in chronic ventricular arrhythmias: a double-blind placebo-controlled crossover study.

Ten patients suffering from chronic premature ventricular complexes (greater than 60/h) were treated orally in a double-blind crossover study with encainide (50 mg three times a day) and disopyramide (200 mg three times a day), with five 7 day study periods: survey, placebo, encainide or disopyramide, washout placebo and disopyramide or encainide. At the end of each 7 day period, a 12 lead electrocardiogram, a 48 hour ambulatory electrocardiogram and a treadmill exercise test were performed. Blood levels of encainide and its metabolites and of disopyramide were measured at the end of each treatment (steady state). Drug efficacy was assessed by: 1) more than 80% reduction in the number of premature ventricular complexes per 24 hours, and 2) absence of ventricular tachycardia. Encainide was effective in four patients (complete suppression of premature ventricular complexes) and ineffective in five. One patient who showed a 92% reduction in the number of premature ventricular complexes developed sustained ventricular tachycardia after 24 hours of treatment. Disopyramide was effective in three patients (greater than 80% reduction in the number of premature ventricular complexes) and ineffective in seven patients. With encainide, the percent increase in PR, QRS and QT interval duration was, respectively: 32.7 (p less than 0.001), 30.8 (p less than 0.001) and 10.6% (p less than 0.01). With disopyramide this increase was not significant. Despite the variability of drug blood levels, a relation between blood levels and suppression of premature ventricular complexes on the 48 hour ambulatory electrocardiogram was found with encainide, but not with disopyramide.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Electrophysiological effects of encainide and its metabolites in 11 patients.

Encainide is a new antiarrhythmic class IC agent. Eleven patients were given 1 mg/kg of encainide i.v. over a 15-min period. Electrophysiological studies were done before and l h after drug administration. Blood levels of encainide and its principle metabolites O-demethyl-encainide, 3 metoxy-O-demetyl-encainide and N-demethyl-encainide were measured serially after drug administration. Heart rate, blood pressure, and conduction intervals were monitored. Sixty minutes after drug administration there was a marked increase of the QRS, PA, AH, and HV intervals of 28.1% (p less than 0.01), 17.2% (p less than 0.01), 22.4% (p less than 0.01), and 32.2% (p less than 0.01), respectively, and a slight increase of the Wenckebach cycle length of 8% (p less than 0.05). BP, RR, QT, CSNRT, ESACT, ERP, and FRP did not vary significantly. The HV interval already was increased significantly 2 min after drug administration, while AH was not increased until 15 min after drug administration. The average blood levels of encainide and ODE 60 min after drug administration were 0.410 +/- 0.12 and 0.176 +/- 0.09 microgram/ml, respectively (mean +/- SE of the mean). There was a positive correlation between the increase of the AH and the blood level of ODE, which points out the importance of prolonged electrophysiological studies when testing drug with possibly active metabolites.

Adult↗
PubMed1990

Comparative hemodynamic effects of procainamide, tocainide, and encainide in severe chronic heart failure.

Many of the newer antiarrhythmic agents are said to cause minimal myocardial depression, but their hemodynamic effects have not been invasively evaluated and compared in patients with severe chronic heart failure. In a randomized, crossover study, the hemodynamic responses to single oral doses of procainamide (750 mg), tocainide (600 mg), and encainide (50 mg) given to 21 patients with severe chronic heart failure were compared. Cardiac performance decreased with all three drugs, but the magnitude of deterioration differed among the three agents. Stroke volume index decreased with procainamide (-5 +/- 1 ml/m2, p less than 0.001), tocainide (-7 +/- 1 ml/m2, p less than 0.001), and encainide (-8 +/- 1 ml/m2, p less than 0.001), but the decline was significantly greater with encainide than with procainamide (p less than 0.05). Similarly, left ventricular filling pressure increased with tocainide and encainide (+4 +/- 1 and +5 +/- 2 mm Hg, respectively; both p less than 0.05), but not with procainamide; the increase was significantly greater with tocainide and encainide than with procainamide (p less than 0.001). These deleterious hemodynamic effects were accompanied by worsening symptoms of heart failure in six patients with encainide and seven patients with tocainide but in only two patients with procainamide. Serum levels for all drugs were in the therapeutic range. In conclusion, although the three type I antiarrhythmic agents tested may all adversely affect left ventricular function in patients with heart failure, encainide and tocainide are more likely than procainamide to cause hemodynamic and clinical deterioration.

Aged↗