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PubMedDate not supplied

Pharmacokinetic and pharmacodynamic analysis of platinum after combined treatment of cisplatin and procainamide hydrochloride in mice bearing P388 leukemia.

BACKGROUND: Our previous studies showed that procainamide hydrochloride may be an important modulator of cisplatin toxicity and antitumour activity. This study was performed in order to investigate if procainamide hydrochloride may influence the therapeutic index of cisplatin by inducing modifications of its pharmacokinetics and pharmacodymanics in vivo. MATERIALS AND METHODS: The pharmacokinetic profile of cisplatin administered either in the presence or absence of procainamide hydrochloride was investigated in BDF1 female mice bearing 6-day P388 leukemia. Procainamide hydrochloride was administered i.v. at the dose of 50 mg/kg, immediately before cisplatin which, in turn, was administered i.p. at the dose of 8 mg/kg. RESULTS: The combined administration of the antiarrhythmic drug and cisplatin caused significant differences in the pharmacokinetic profiles of Pt in plasma, ascites fluid and tissues. Filterable Pt was significantly increased both in plasma and ascites fluid in animals given the combined treatment. Similarly, a small increase was also found for total plasma Pt. These differences caused some changes of the pharmacokinetic parameters of filterable (plasma: AUC0-1 h = +16%, t1/2 alpha = +29%, t1/2b = +14%, K2p = -32%; ascites fluid: AUC0-1 h = +23%, t1/2 alpha = +78%, t1/2 beta = -49%, and total Pt (plasma: AUC0-1 h = +19%, t1/2 alpha = +27%, t1/2 beta = -22%; ascites fluid: AUC0-1 h = +6%, AUC0-infinity = +43%, t1/2 alpha = +30%). The analysis of tissue Pt content showed the general increase of Pt concentration in the main organs of animals treated with cisplatin and procainamide hydrochloride, with AUC0-24 h increased by 95%, 22%, 90% and 28% in kidney, liver, spleen and lung, respectively. The analysis of binding of Pt to DNA and percent interstrand cross-links (%ISCL) in P388 tumour cells showed that the % ISCL (10.44 +/- 3.81% vs. 3.51 +/- 0.01%) and the efficiency of ISCL formation (0.51 +/- 0.14 vs. 0.17 +/- 0.02 %ISCL.microgram DNA/pg Pt) were significantly greater when cisplatin was administered in association with procainamide hydrochloride. CONCLUSION: Our results show that procainamide hydrochloride may alter the pharmacodynamics and the pharmacokinetics and distribution of Pt in tumored mice treated with cisplatin.

Animals↗
PubMedDate not supplied

Comparative metabolism and covalent binding of procainamide by human leukocytes.

Activated neutrophils and monocytes were found to metabolize procainamide to a reactive hydroxylamine. In contrast, there was little or no metabolism by lymphocytes or platelets. Therefore, it appears that only leukocytes that contain myeloperoxidase can metabolize procainamide to a significant degree. There was no difference in the degree to which neutrophils from males or females metabolized procainamide; however, monocytes from males formed significantly more hydroxylamine than did monocytes from females. By use of radiolabeled procainamide, covalent binding of procainamide to leukocytes was detected, and the degree of binding correlated with the cells' ability to oxidize procainamide. These findings suggest that myeloperoxidase is the major enzyme involved in the formation of reactive metabolites by leukocytes, a pathway that we propose may be responsible for procainamide-induced lupus and agranulocytosis.

Binding Sites↗
PubMed1986

Pharmacokinetics of procainamide hydrochloride in dogs.

Pharmacokinetics of procainamide hydrochloride were studied in 2 groups of dogs. In a group of 6 dogs, procainamide was administered IV at a small dose of 8 mg/kg (group 1), and blood samples were obtained for 3.5 hours. In another group of 6 dogs, procainamide was administered IV and orally at an average dose of 25.5 mg/kg (group 2) in a crossover manner. Blood samples were obtained for 48 hours. In 2 dogs (previously used in part II), N-acetylprocainamide (NAPA) was administered IV at a dose of 10 mg/kg. Plasma samples were assayed for procainamide by fluorescence polarization immunoassay, and NAPA samples were assayed by high-performance liquid chromatography. In group 1, the elimination of procainamide was described by a 1-compartment, open pharmacokinetic model. The elimination half-life was 2.43 hours, the apparent volume of distribution was 1.44 L/kg, and the systemic clearance was 0.412 L/kg/hr. In group 2, 2 of the 6 dogs were described by a 1-compartment model, and 4 of the 6 dogs were described with a 2-compartment pharmacokinetic model. The elimination half-life for the IV dosage was 2.85 hours, the apparent volume of distribution was 2.13 L/kg, and the systemic clearance was 0.519 L/kg/hr. For the orally administered dose, the bioavailability was 85%, and the absorption half-life was 0.5 hours. There was no evidence of acetylation of procainamide to NAPA or deacetylation of NAPA to procainamide. The estimated elimination half-life of NAPA was 4.7 hours.

Acecainide↗
PubMed1988

Procainamide administration during electrophysiology study--utility as a provocative test for intermittent atrioventricular block.

The utility of procainamide, up to 10 mg/kg IV, as a provocative test for intermittent high degree atrioventricular (AV) block was evaluated in a total of 89 patients. Forty two patients had resting 1:1 AV conduction but had bifascicular block and a history of syncope. High degree AV block had not been documented in anyone. Before procainamide, the HV interval was greater than 60 ms in 17 of the 42 patients but no patient developed infra-Hisian block with fixed rate atrial pacing or following programmed atrial extrastimuli. Procainamide administration lengthened the mean HV interval by 11.9 ms and in seven (14%) the HV increment was marked, 15-75 ms. Furthermore, four (9.5%) of these 42 patients developed second or third degree infra-Hisian block and in two of these four patients, the HV prior to procainamide administration was normal or only mildly prolonged (less than 60 ms). The findings were compared to those in three "control" groups. Among four patients with bifascicular block, previously documented transient AV block but 1:1 AV conduction at the time of study, three developed high degree AV block following procainamide. Among five patients with bifascicular block but without syncope nor documented high degree AV block, the mean HV interval lengthened by 18.8 ms and in three the HV increment was 24-30 ms. In another 38 patients with neither syncope nor an intraventricular conduction defect, the mean HV interval lengthened by 5.3 ms and in two cases by 20-25 ms. Most importantly, high degree AV block was never observed in the latter two groups. During follow-up of up to 10 years (mean 46 months), three of the seven patients in whom procainamide provoked high degree AV block have subsequently progressed to fixed complete AV block. Although the incidence of provocation of AV block was relatively low, it was concluded that, among patients with possible intermittent AV block, administration of procainamide as a test of distal conduction has limited value but is still useful, and may provide information additional to that obtained from mere assessment of the HV interval.

Adolescent↗
PubMed1989

Trimethoprim inhibition of the renal clearance of procainamide and N-acetylprocainamide.

To test the effect of trimethoprim (an antibiotic commonly administered with sulfamethoxazole) on the disposition of the antiarrhythmic procainamide hydrochloride and its active metabolite N-acetylprocainamide, 10 healthy men received 1 g of procainamide hydrochloride orally on two occasions, coadministered with placebo or trimethoprim (100 mg twice a day for 2 days before and then 200 mg with the procainamide dose). Trimethoprim decreased the mean (+/- SD) renal clearance by 45% after the dose of procainamide was administered (487 +/- 129 vs 267 +/- 123 mL/min) and that of N-acetylprocainamide by 26% (275 +/- 78 vs 192 +/- 82 mL/min) compared with placebo. The mean area under plasma concentration--time curve 0 to 12 hours after dosing increased 39% for procainamide (19.8 +/- 4.8 vs 27.6 +/- 7.2 mg.h/L) and 27% for N-acetylprocainamide (9.1 +/- 2.1 vs 11.4 +/- 2.8 mg.h/L). The corrected QT electrocardiographic interval at 2 hours after the procainamide dose was 0.40 +/- 0.02 second with placebo and 0.43 +/- 0.03 second with trimethoprim. Trimethoprim may increase procainamide and N-acetylprocainamide plasma concentrations, resulting in increased pharmacodynamic response apparently caused by the competition for renal tubular cationic secretion.

Acecainide↗
PubMed1988

The influence of ethanol on pharmacokinetic parameters of procainamide in rabbits.

The effect of ethanol on procainamide pharmacokinetics was investigated in rabbits. Procainamide was injected iv in a dose of 13 mg.kg-1 together with ethanol in doses of 0.1, 0.5 or 1.0 g.kg-1.h-1. In another experiment procainamide was given in a dose of 40 mg.kg-1 together with ethanol in a dose of 1.0 g.kg-1 p.o. The third group of rabbits received procainamide in the form of 1 tablet 0.25 g together with ethanol in a dose of 1.0 g.kg-1 p.o. Ethanol shortened biological half-life of procainamide elimination, increased the value of the rate constant of elimination and procainamide clearance. Concomitant oral administration of ethanol and procainamide decreased the peak plasma concentration and decreased the area under the drug level curve.

Administration, Oral↗
PubMed1995

IgG but not other classes of anti-[(H2A-H2B)-DNA] is an early sign of procainamide-induced lupus.

A longitudinal study was undertaken to characterize the autoantibodies induced during the course of procainamide treatment and to relate this information to the appearance of symptomatic drug-induced lupus. IgG, IgA, and IgM Abs to histones, native and denatured DNA, chromatin, and (H2A-H2B)-DNA were determined by ELISA in serial serum samples obtained over the course of an average of 2.1 yr on 22 patients undergoing treatment with procainamide and on an additional 9 patients after discontinuation of procainamide because of drug-induced lupus. Ten patients in the prospective group developed lupus-like symptoms after an average of 1.8 +/- 2.1 yr of procainamide treatment. Of the total of 19 patients with drug-induced lupus, 16 had IgG Abs to the (H2A-H2B)-DNA complex at the time of diagnosis; this autoantibody was first detected 0.9 +/- 1.3 yr before diagnosis in 7 patients. In contrast, the 9 patients who remained asymptomatic during treatment with procainamide for an average of 4.3 +/- 2.2 yr had negligible levels of IgG anti-[(H2A-H2B)-DNA], although IgA and IgM Abs of this specificity were not uncommon. Abs to denatured DNA and histones were elicited coordinately, but these specificities did not discriminate symptomatic from asymptomatic procainamide-treated patients. We conclude that chronic exposure to procainamide commonly elicited autoantibodies with specificities for denatured epitopes on DNA and histones and for native regions on the (H2A-H2B)-DNA subunit of chromatin. However, rapid switch to the IgG class of anti-[(H2A-H2B)-DNA] occurred only in patients who went on to develop symptomatic disease.

Antibodies, Antinuclear↗
PubMed1975

Acetylation of procainamide in man and its relationship to isonicotinic acid hydrazide acetylation phenotype.

To assess the extent of the acetylation of procainamide (PA) to N-acetylprocainamide (NAPA) in man, and its relation to isonicotinic acid hydrazide (INH) acetylation phenotype, the following study was done. Fourteen subjects received 500 mg of PA - HCL orally. INH acetylation phenotype was determined by the serum half-life of INH after 4 mg/kg of INH orally. Each urine voided for 96 hr after procainamide was saved and levels of procainamide and NAPA measured by gas-liquid chromatography. The 14 subjects eliminated 52 plus or minus 4 percent of the dose as procainamide and 16 plus or minus 2 percent of the dose as NAPA. Four fast INH acetylators eliminated 23 plus or minus 3 percent of the dose as NAPA compared to 12 plus or minus 1 percent by the slow acetylators (p smaller than 0.05). The amount of unaltered procainamide excreted by the fast and slow INH acetylators was not significantly different, 50 plus or minus 4 percent and 53 plus or minus 4 percent, respectively. Of the total amount of drug recovered in the urine of the fast and slow INH acetylators, NAPA accounted for 32 percent and 19 percent, respectively (p smaller than 0.01). There appears to be a positive correlation between the ability to acetylate INH and the ability to acetylate procainamide.

Acetylation↗
PubMed1978

Metabolism of procainamide in patients with chronic heart failure, chronic respiratory failure and chronic renal failure.

Fractional hydrolysis and acetylation of procainamide, acetylation of procainamide-derived p-aminobenzoic acid and plasma hydrolysis of procaine were studied in 20 patients with chronic heart failure (CHF), 20 patients with chronic respiratory insufficiency (CRI) and 20 patients with chronic renal failure (RF). The results were compared with those obtained in a group of 20 normal volunteers. Hydrolysis of procainamide and procaine were reduced in patients with CHF and CRI, but not in patients with RF. Moreover, more marked decreases in procainamide and procaine hydrolysis were seen in subgroups with secondary hepatic dysfunction. The diminution of hydrolysis of procainamide was not paralleled by changes in acetylation of procainamide or p-aminobenzoic acid. It is concluded that in patients with hepatic involvement secondary to advanced CHF or CRI, hepatic and plasmatic hydrolysis activity is decreased to a degree equivalent to primary liver failure.

Acetylation↗
PubMed1993

Management of atrial tachyarrhythmias in the critically ill: a comparison of intravenous procainamide and amiodarone.

OBJECTIVE: To compare the efficacy and safety of intravenous (IV) amiodarone and procainamide for the treatment of atrial tachyarrhythmias (AT) in the critically ill. DESIGN: In this prospective study, patients were allocated to drug treatment on the basis of hospital identification number, even for procainamide and odd for amiodarone. SETTING: Patients were recruited from a teaching hospital ICU and did not include postoperative cardiac patients. PATIENTS AND PARTICIPANTS: 26 patients with AT sustained for at least 1 h and failure to respond to correction of possible precipitating factors were entered in the study. Exclusion criteria were systolic blood pressure (SBP) < 80 mmHg, and known hypersensitivity to either drug. Two patients with chronic atrial fibrillation (who received amiodarone) were later excluded from the analysis. In the final analysis, 14 patients received procainamide and 10 amiodarone. INTERVENTIONS: IV amiodarone (3 mg/kg followed by 10 mg/kg/24 h, with repeat dose of 3 mg/kg at 1 h if no response) or i.v. procainamide (10 mg/kg at 1 mg/kg/min followed by infusion of 2-4 mg/min for 24 h, with repeat dose of 5 mg/kg at 1 h if no response). MEASUREMENTS AND RESULTS: In the procainamide group 10/14 (71%) and in the amiodarone group 7/10 (70%) had converted to sinus rhythm by 12 h. There was no significant difference in response between the groups. SBP was not significantly different from baseline after administration of either drug. CONCLUSIONS: Procainamide and amiodarone appear to be safe and equally effective in the treatment of AT in the critically ill.

Aged↗
PubMed1993

Modulation of procainamide toxicity by selenium-enriched yeast in rats.

Free radical processes are proposed to play a crucial role in the development of procainamide adverse effects. Therefore, selenium, as a potent antioxidant, may modified procainamide toxicity. To test this hypothesis plasma and liver thiobarbituric acid-reacting substances (TBARS), plasma antioxidant activity (AOA), erythrocyte and liver superoxide dismutase (SOD), catalase, as well as selenium-dependent glutathione peroxidase (Se-GPX) were determined in the following four groups of rats: selenium-treated (Se), procainamide-treated (P), procainamide and selenium-treated (P + Se), and control (C). Morphological studies of leukocytes [tested for lupus erythematosus (LE) cells] and liver were also made. Atypical, i.e. enlarged and swollen, leukocytes resulting from procainamide and selenium treatment were observed. These changes were found in four out of five rats in the Se group, eight out of ten in the P group, and in seven out of ten in the P + Se group. LE-like cells were observed in two rats in the P + Se group. A statistically significant decrease in plasma and liver TBARS by 20% and 36%, respectively, increased activity of SOD by 20%, catalase by 48% and Se-GPX by 15% in erythrocytes, and decreased activity of liver SOD by 17% and catalase by 22% were found in the P + Se group as compared to the P group. These results indicated that selenium exerted antioxidant effects on the procainamide-treated rats. However, selenium did not prevent the development of disturbances in leukocyte morphology, on the contrary, it possibly promoted the conversion of leukocytes to LE cells.

Animals↗
PubMed1987

The effect of procainamide on plasma cholinesterase activity.

The in vitro effect of procainamide on plasma cholinesterase (PCHE) activity in the plasma of ten normal ASA physical status I patients was studied using a kinetic method. The mean plasma cholinesterase activity without procainamide (control) was 0.90 +/- 0.09 units.ml-1. The dibucaine numbers of all the samples were in the normal range of 78 to 86, indicating normal genotypes. The mean plasma cholinesterase activity, in the presence of procainamide in concentrations of 5.0, 10.0, 20.0 and 40.0 micrograms.ml-1, was reduced to 0.73 +/- 0.04, 0.61 +/- 0.03, 0.45 +/- 0.02, and 0.36 +/- 0.01 units.ml-1, respectively. At therapeutic concentrations of 4 to 12 micrograms.ml-1, procainamide inhibited cholinesterase activity 15 to 30 per cent. The authors also showed that the concentration of procainamide required to inhibit 50 per cent of plasma cholinesterase activity was 20 micrograms.ml-1 (I50). The authors conclude that procainamide when tested in vitro had a statistically significant depressant effect on plasma cholinesterase activity at all the concentrations studied.

Adult↗
PubMed2005

Quinidine and procainamide inhibit murine macrophage uptake of apoptotic and necrotic cells: a novel contributing mechanism of drug-induced-lupus.

UNLABELLED: A number of mechanisms have been proposed to explain the etiology of drug-induced lupus (DIL) but the effect of apoptotic and necrotic cell handling has not been previously examined. OBJECTIVE: To evaluate the effect of quinidine and procainamide at therapeutic range concentrations, on the uptake of apoptotic and necrotic thymocytes by murine peritoneal macrophages and on macrophage survival, as a novel mechanism for DIL. METHODS: Thymocytes were stained and induced to undergo apoptosis by serum withdrawal. Apoptosis was evaluated using annexin V and propidum iodide (PI) and PI staining. Necrosis was induced by heating. Peritoneal macrophages were treated with quinidine or procainamide at a range of therapeutic concentrations and incubated with stained apoptotic and necrotic thymocytes. Apoptotic and necrotic cell uptake was evaluated by flow cytometry using double staining of thymocytes and macrophages and by confocal microscopy. Green fluorescent latex beads were used as controls for phagocytosis. RESULTS: Significantly decreased uptake of apoptotic and necrotic cells was seen in the presence of quinidine and procainamide. The documented effect was mainly on the number of apoptotic/necrotic cells per macrophage. Uptake of fluorescent latex beads offered to resident macrophages was not significantly affected by quinidine or procainamide. No pro-apoptotic effect of quinidine or procainamide on macrophages was seen. CONCLUSION: Quinidine and procainamide at therapeutic range concentrations specifically inhibit clearance of apoptotic and necrotic cells by peritoneal macrophages. Altered handling of apoptotic and necrotic cells may represent a contributing mechanism for DIL.

Animals↗
PubMed1982

Electrophysiologic effects of procainamide on sinus function in patients with and without sinus node disease.

To compare the effects of procainamide on sinus node (SN) function in the presence (seven patients) and absence (nine patients) of SN dysfunction, sinus cycle length (SCL), maximal corrected sinus recovery time (maximal CRST), paced cycle length yielding peak SN suppression (PCLp), and indirect sinoatrial conduction time (SACT) were determined before and after intravenous administration of 10 to 15 mg/kg procainamide in each patient. Plasma procainamide concentration was in the therapeutic range in all patients. The mean SCL did not change significantly in either group (-24 +/- 58 and -73 +/- 171 msec for patients with normal and abnormal SN function, respectively). The maximal CSRT shortened 136 +/- 112 msec (p less than 0.01) in the group with normal SN function (nine of nine patients)( but tended to lengthen 85 +/- 95 msec (p less than 0.10) in the group with SN dysfunction (six of seven patients). PCLp shortened in only two of nine of the normal group but tended (NS) to shorten in five of seven patients with SN dysfunction. We conclude that in the absence of SN disease, procainamide does not adversely affect SN function. In apparent contrast in patients with SN dysfunction, procainamide tended (NS) to prolong CSRT and seemed (NS) to enhance conduction in the sinoatrial junction (PCLp and SACT both declined). The occasional lengthening of CSRT implies that procainamide might prolong post-tachycardia pauses and thus could worsen symptoms in certain patients with the bradycardia-tachycardia syndrome.

Adult↗
PubMed1985

Comparative efficacy of oral sotalol and procainamide in patients with chronic ventricular arrhythmias: a multicenter study.

In an open, randomized, crossover study, the efficacy of sotalol and procainamide was compared in 33 patients with frequent, chronic premature ventricular contractions (PVCs). A 75% reduction in PVCs/24 hours (two 24-hour recordings) was arbitrarily considered to constitute an adequate therapeutic effect. Sotalol was started at a dose of 160 mg once daily for 1 week, followed by a 24-hour recording. In the absence of any therapeutic effect, the same procedure was repeated with 320 mg, 480 mg, and 640 mg daily. Procainamide, 1 gm three times/day, was given or, if plasma concentrations were insufficient, 1.5 gm three times/day for 1 week. PVC control was obtained in 22 (67%) patients on sotalol, including all 12 with ischemic heart disease. Procainamide was successful in 13 (39%) patients. Effects on the number of attacks of ventricular tachycardia were achieved by both drugs in those patients where PVCs were reduced by at least 75%. Sotalol caused side effects in five patients, who therefore could not accept planned increases in dosage. Side effects were noted by 12 patients with procainamide. Nine patients responded to both drugs, seven to neither. Thirteen responded to sotalol only and four to procainamide only. We conclude that sotalol is a useful alternative to procainamide in controlling chronic PVCs, especially in patients with ischemic heart disease.

Adult↗
PubMed1986

Antiarrhythmic drug efficacy at electrophysiology testing: predictive effectiveness of procainamide and flecainide.

In an effort to assess the ability of procainamide to predict effectiveness of antiarrhythmic agents at programmed electrical stimulation (PES) testing, we compared the result of procainamide at PES testing with that of all of the other agents studied. One hundred fifty-three patients underwent PES studies because of either sustained or nonsustained ventricular tachycardia (VT). Procainamide prevented VT induction in 79 of 153 patients. Seventy-four of the remaining 153 were inducible for VT on procainamide, with 55 of these being protected by another antiarrhythmic agent (p less than 0.001). If procainamide failed to prevent VT induction, other conventional and experimental agents were equally as likely to be effective in preventing VT induction. Analysis of flecainide acetate as a predictor of efficacy was also evaluated. Fifty-five patients received flecainide and 29 of these were protected at PES testing; 26 of these patients were also protected with another agent. When VT was inducible in patients who received flecainide, 15 of these 26 patients were protected by another agent, either conventional or experimental (p less than 0.01). Thus, if procainamide or flecainide prevented VT induction they accurately predicted effectiveness of other drugs; however, when they did not prevent VT induction, they served as a poor predictor of the possible effectiveness of other drugs. Serial drug testing at PES studies with multiple conventional and experimental drugs increases the likelihood of finding an effective antiarrhythmic agent.

Anti-Arrhythmia Agents↗
PubMed1987

Immunohistochemical localization of procainamide in normal, ischemic, and necrotic canine myocardium during acute experimental myocardial infarction.

This report represents the first application of immunohistochemical methods for localizing an exogenously administered drug. Intravenously administered procainamide was localized in normal, ischemic, and necrotic myocardium in 23 dogs. Rabbit antiprocainamide antibodies were used in an avidin-biotin-peroxidase complex staining method. Normal myocardium demonstrated diffusely positive immunostaining for procainamide, as did the cardiac conduction system and vascular endothelial cells. Necrotic myocardium demonstrated markedly reduced to absent immunostaining. By contrast, in regions of myocardial ischemia without necrosis, immunostaining for procainamide was similar to that in the normal myocardium. Procainamide myocardial tissue levels were reduced in necrotic and ischemic zones compared to normal (p less than 0.05) only in those animals in which procainamide was administered after rather than before the onset of coronary occlusion. The demonstration of the absence of drug binding in the necrotic cells suggests that myocardial tissue levels or radiolabelled assessment of drug distribution can be misleading when nonhomogeneous tissue is sampled. The immunohistochemical technique provides additional information about the regional and cellular distribution of procainamide that is complementary to the information obtainable by radiolabelling microspheres and from biochemical assays.

Animals↗
PubMed1995

Multicenter trial of sotalol compared with procainamide in the suppression of inducible ventricular tachycardia: a double-blind, randomized parallel evaluation. Sotalol Multicenter Study Group.

Sotalol is the prototype class III agent that combines beta-blocking properties with the propensity to prolong the effective refractory period by lengthening the action potential duration. Its precise effect on the prevention of ventricular tachycardia-ventricular fibrillation (VTVF) compared to class I agents has not been evaluated in a blinded study. In a double-blind parallel-design multicenter study, the electrophysiologic and antiarrhythmic effects of intravenous and oral sotalol (n = 55) and procainamide (n = 55) were therefore compared in patients with VTVF inducible by programmed electric stimulation. Sotalol produced a greater effect on lengthening the ventricular effective refractory period (VERP). It prevented the inducibility of VTVF in 30% versus 20% for procainamide, but this was not significantly different. In an alternate therapy group (n = 41) of similar patients previously refractory to or intolerant of procainamide, intravenous sotalol prevented inducibility in 32%. The pooled overall sotalol efficacy rate was 31%. There was a significant relation between the increase in the VERP and the prevention of inducibility of VTVF (n = 56; p < 0.02). VERP of > or = 300 msec was critical for the prevention of VTVF inducibility. Thirteen sotalol and 6 procainamide responders from the randomized group and 30 from the nonrandomized groups completed 1 year of oral sotalol therapy follow-up. Life-table analysis of these patient in each group showed a trend in favor of sotalol; however, statistical analysis was not possible because of the small numbers of patients. Both sotalol and procainamide were well tolerated. In the randomized group there was one case of sudden death during treatment with sotalol and two cases of nonfatal torsades de pointes in the procainamide group and two in the sotalol group; in the nonrandomized alternate therapy group, there were 6 cases of nonfatal torsades de pointes. The data support the emerging role of sotalol in the control of symptomatic ventricular tachycardia and fibrillation.

Administration, Oral↗