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PubMedDate not supplied

[Preventive disopyramide in patients with ventricular arrhythmias detected by exercise].

Twenty patients with coronary heart disease subjected to exercise testing presented ventricular arrhythmias. In a "double blind" design, oral disopyramide was administered during 7 days, after which the test was repeated. In 16 patients disopyramide prevented the appearance of arrhythmia or decreased their severity. Basal heart rate increased. Significant toxic or colateral effects were not observed. In 6 cases, placebo also hindered exercise arrhythmias. It is suggested that disopyramide may be useful in the prevention of sudden death from ventricular arrhythmias.

Adult↗
PubMed1994

Comparative analysis of electrophysiologic effect of metoprolol and disopyramide, acting alone or in combination in patients with supraventricular tachycardia and Wolff-Parkinson-White syndrome.

In the aim of determining an electrophysiologic effect of disopyramide and metoprolol at alone therapy and in combination in patients with supraventricular tachycardia on the background of Wolff-Parkinson-White syndrome 23 persons were examined. All patients were subjected to an intracardiac electrophysiological testing; in its process metoprolol in the dosage of 0.2 mg/kg of body weight, disopyramide in the dosage of 2 mg/kg per body weight both separately and in combination were controlled. It was identified that metoprolol and disopyramide are an effective antiarrhythmic preparates applied for arresting and prevention of reciprocating orthodromic tachycardias in patients with Wolff-Parkinson-White syndrome.

Adult↗
PubMed1993

[Efficacy and tolerability of sustained-release disopyramide in the treatment of cardiac arrhythmia. Results of a study with 593 patients].

In the context of an open multicentre study, 593 patients participated in the evaluation of sustained release disopyramide (*) in the treatment of cardiac arrhythmias. One hundred and seventy one (29%) had a ventricular arrhythmia, 382 (64%) a supraventricular arrhythmia and 40 (7%) an atrial and ventricular arrhythmia. Two hundred and seventy patients (46%) had underlying cardiac disease. Disopyramide was administered at the mean daily dose of 462 +/- 95 mg. The effectiveness of treatment was assessed after 3 and 6 months by Holter in the group treated for ventricular arrhythmias, the responder rate was 52.6% at three months and 58.1% at 6 months. It was significantly (p < 0.001) greater in the group treated for supraventricular arrhythmias (71.3% at 3 months and 82.1% at 6 months). The Holter responder rate in patients aged over 65 (70.5% at 6 months) was high and general and cardiac acceptability similar to that in younger patients. Adverse events led to the interruption of treatment in 8.2% of patients. Thus the effectiveness/acceptability ratio of SR disopyramide makes it entirely appropriate for the treatment of cardiac arrhythmias, even in the elderly.

Adult↗
PubMed1977

Disopyramide phosphate: tissue uptake and relationship between drug concentrations in the plasma and myocardium of rats.

Tissue uptake of total-14C and disopyramide (DP) was examined in rats following 5 to 100 mg/kg doses of [14C]-disopyramide phosphate [14C-DPP]. Disopyramide was the major 14C constituent in the plasma or tissues. The gastrointestinal absorption of [14C]-DPP was 86% as determined from the areas under the plasma total-14C concentration-time curves following 10 mg/kg oral or i.v. administration. Total-14C was widely distributed in tissues, and at 2 hr the highest uptake occurred in the fat, liver and spleen giving concentrations ranging from 7 to 15 times that in plasma. In the thymus, adrenals, lungs, salivary glands, testes and muscle the concentrations were about twice that in plasma, in the heart and eyes similar to that in plasma, and in the brain less than one-third that in plasma. The uptake and elimination characteristics of total-14C or DP in plasma and myocardium were similar. The two-hour plasma or myocardium DP concentrations were linearly related to the oral dose in the 5 to 50 mg/kg range. In three days about 30% (oral) and 39% (i.v.) of the 14C dose (10 mg/kg) was excreted in the urine, 64% (oral) and 54% (i.v.) in the feces, and less than 2.1% remained in the carcass. The composition of the urinary and fecal metabolites was similar after oral or i.v. administration of the drug.

Administration, Oral↗
PubMed1998

[A patient with disopyramide intoxication rescued by percutaneous cardiopulmonary support].

A 28-year-old man was admitted to our hospital in a hypotensive state 2 hours after taking 8,400 mg disopyramide. Infusion of catecholamine and gastric lavage restored normal blood pressure. However, 8 hours after taking the disopyramide he became hypotensive again and electrocardiographic findings revealed bizarre ventricular complexes resulting in ventricular flutter. Although standard cardiopulmonary resuscitation was not effective, his circulatory status was maintained by percutaneous cardiopulmonary support (PCPS). After 36 hours electrocardiography showed sinus rhythm, and his cardiac function became normal. Patients with severe cardiac dysfunction or cardiac arrest caused by disopyramide intoxication can be supported by PCPS until cardiac function is restored.

Adult↗
PubMed1998

[A randomized double-blind trial comparing cibenzoline and disopyramide in the prevention of recurrences of atrial tachyarrhythmia].

The aim of this multicenter, randomised, double-blind trial was to compare the efficacy and tolerance of oral disopyramide (D: 250 mg slow release twice daily) compared with cibenzoline (C: 130 mg twice daily) in the prevention of recurrences of atrial arrhythmias over a 6 month period. Sixty patients (mean age: 62 +/- 14 years; 37 men, 23 women; cardiac disease in 60% of cases) were randomised to two groups: C (N = 31) and D (N = 29). The commonest arrhythmia was atrial fibrillation (83%). The arrhythmia was recent (< 3 months) in 41% of patients and present for more than one year in 38% of patients. Sixteen patients of Group C (52%) and 11 of Group D (38%) had recurrences after an average of 79 +/- 58 days for Group C and 58 +/- 40 days for Group D (p = NS). The probability of absence of recurrence at 6 months was 36 +/- 11% in Group C and 55 +/- 10% in Group D (p = NS). Four patients in Group C (13%) and 13 patients in Group D (45%) had at least one unwanted side-effect (p = 0.009). Treatment was stopped because of side-effects in 2 patients in group C (6%) and 6 patients in Group D (21%). These results show that cibenzoline has a comparable efficacy for the prevention of recurrence of atrial tachyarrhythmia and is significantly better tolerated than disopyramide. This differences is mainly related to the marked anticholinergic effects of disopyramide.

Aged↗
PubMedDate not supplied

Influence of concentration-dependent protein binding on serum concentrations and urinary excretion of disopyramide and its metabolite following oral administration.

Concentrations of disopyramide (D) and mono-N-dealkyldisopyramide (MND) were measured in serum and urine following administration of 100, 150, 200, and 300 mg D to four volunteers. The free fraction of D in serum was drug concentration-dependent in all four subjects following the administration of the four doses. Areas under the free (unbound) D serum concentration-time curves (AUC free 0-9) were linearly related to dose following 100-200 mg D. AUC free 0-9 values were 30-60 per cent higher than expected in two subjects following 300 mg D due to an apparent dose-dependent decrease in D renal tubular secretion. Renal clearance of free D averaged 10.9 1 h-1. The renal clearance of MND averaged 10.3 1 h-1. The urinary excretion of MND was proportional to disopyramide dose.

Administration, Oral↗
PubMed1997

Enantioresolution of disopyramide by capillary affinity electrokinetic chromatography with human alpha1-acid glycoprotein (AGP) as chiral selector applying a partial filling technique.

A method using alpha1-acid glycoprotein (AGP) as chiral selector for disopyramide by means of affinity electrokinetic chromatography has been developed. In order to avoid UV absorbance interferences, less than the effective length of the capillary was filled with the chiral selector. The electrophoretic conditions were chosen to give opposite migration directions for the chiral selector and the analyte; AGP migrated away from the detector. Enantiomers of disopyramide were separated on a methylcellulose-coated capillary with 20 cm length to the detector. The enantioresolution of the solute was affected by the concentration of the chiral selector, the plug length of the selector in the capillary, and the applied voltage. Resolution factors and migration times decreased with reduction of the plug length, while the efficiency of the separation system and peak performance were improved by decreasing the separation zone. A special feature of the technique is an enhanced selectivity due to increasing separation of the enantiomers when the fastest has migrated from the selector zone, while the second one still is retained. Equations relating selectivity and resolution with the difference in effective plug lengths between the two enantiomers are developed. Optimized conditions yielding complete resolution, requiring an 0.75 mM AGP plug of only 4.5 cm effective length, also gave high efficiencies (about 400,000 plates/m) for both enantiomer peaks.

Chromatography↗
PubMed1989

Clinical pharmacokinetics of levorotatory and racemic disopyramide, at steady state, following oral administration in patients with ventricular arrhythmias.

Electrophysiological effects, antiarrhythmic activity and kinetics of levorotatory disopyramide (R(-) DP) and racemic disopyramide (equimolar mixture of R(-) DP and S(+) DP) were compared in patients with ventricular arrhythmias. This double blind cross-over randomized trial was achieved, at steady-state, following oral administration of 200 mg three times a day. In comparison with baseline values, electrophysiological data indicated that R(-) DP and racemic DP prolonged, significantly and similarly, PR interval (+11.7% and +10%, respectively, P less than .01), and QTc interval (+9.2% and +7%, respectively, P less than .001), while QRS interval was not significantly affected. The antiarrhythmic activity, assessed by percent reduction in ventricular extrasystoles frequency, showed a similar efficiency of levorotatory and racemic DP: 80% and 74%, respectively (P = .24). Ventricular tachycardias disappeared with both treatments in the three patients concerned. During the racemic period, the mean total plasma clearance, expressed as CL/F, of S(+) DP (114.6 ml/min), was significantly lower than that of R(-) DP (157 ml/min), (P less than .001). The mean total plasma clearance of R(-) DP, during the levorotatory period (163 ml/min), did not differ from the respective value determined during the racemic period (P = .32). During the racemic period, the stereoselective difference in total plasma clearances, which is not observed when DP enantiomers are administered separately, may result from an increase in unbound fraction of R(-) DP, due to the presence of S(+) DP, which is known to be a potent displacer of R(-) DP.

Administration, Oral↗
PubMed1995

Alpha-1-acid glycoprotein concentration and the protein binding of disopyramide in healthy subjects.

Age- and gender-related changes in serum alpha 1-acid glycoprotein (AAG) concentration and the serum protein binding of disopyramide were examined after intensive medical examination. Based on the clinical chemistry tests over 51 points, 245 subjects were diagnosed as healthy and 71 subjects (22.5%) revealed an abnormal value for at least one item. In the healthy subjects, serum AAG concentration in men was significantly higher than in women (men, 0.78 +/- 0.18 mg/mL, mean +/- SD; women, 0.67 +/- 0.16 mg/mL). In contrast, there were no significant differences in the AAG concentration between age groups for men and women and in the unbound fraction of disopyramide. Gender changes AAG concentration. Age, however, does not change AAG concentration and the protein binding of the basic drug.

Adolescent↗
PubMed1975

Effect of pKb on lipophilic binding of disopyramide derivatives to human plasma.

The extent of plasma binding, the partition coefficient, and the pKb of 13 disopyramide derivatives were determined. The structural variation on the diisopropylaminoethyl group of disopyramide molecules influenced these physical parameters to varying degrees. Results demonstrated that the extent of interaction between drugs and human plasma was a linear function of their lipophilicity and inversely proportional to the magnitude of the pKb value.

Blood Proteins↗
PubMed1979

Sensitive high-pressure liquid chromatographic determination of disopyramide and mono-N-dealkyldisopyramide.

A high-pressure liquid chromatographic procedure for the accurate determination of disopyramide and its chief metabolite in plasma is presented. The method is suitable for monitoring patients receiving disopyramide therapy. A reversed-phase cyanopropylsilane column is utilized with a mobile phase of 50% acetonitrile and 50% 0.01 M sodium acetate buffer at pH 4.0. Absorption was monitored at 254 nm with a detection limit of 0.2 microgram/ml of plasma. The reproducibility and precision of the procedure were demonstrated on samples containing 0.50-12 microgram/ml of plasma.

Chromatography, High Pressure Liquid↗
PubMed1991

Comparison of the bioavailability of two slow release preparations of disopyramide.

The bioavailability of two slow release preparations of disopyramide has been compared in a randomized cross-over trial of Rythmodan L.A. 250 mg b.d. and Dirytmin Durettes 300 mg b.d., given to 10 healthy volunteers. The plasma concentrations of disopyramide were measured on the 5th day of each treatment period. With both preparations, plasma concentrations were well sustained. The amount absorbed was slightly lower after Rythmodan L.A. than after Dirytmin Durettes, but the fluctuations over a dosing interval were significantly more pronounced for Dirytmin Durettes than for Rythmodan L.A.

Adult↗
PubMed1985

The acute changes in serum binding of disopyramide and flecainide after myocardial infarction.

In the serum basic drugs are principally bound to alpha1-acid glycoprotein (AAG). Following acute myocardial infarction it has been shown that the levels of AAG rise. The serum levels of total protein, albumin, AAG and the protein binding of 2 antiarrhythmic drugs which are bases, disopyramide and flecainide, was measured in vitro with blood samples from eleven patients taken over the first 5 days following myocardial infarction. Mean AAG levels significantly increased from 1.04 g/l on Day 1 to 1.80 g/l on Day 5. The binding of disopyramide, which is highly bound, rose from 80% to 87%, representing a 35% decrease in free drug concentration. In contrast the binding of flecainide fell from 61% to 53%, a 20% increase in free drug concentration. These data suggest that although the binding of strongly bound drugs responds appropriately to increases in binding protein after acute myocardial infarction, poorly bound drugs are displaced from binding sites possibly by endogenous substances. Since the pharmacological effects of a drug are related to its free (unbound) concentration, the changes in the proportions of free to bound drug after myocardial infarction may have important clinical implications.

Aged↗
PubMed1988

Does alpha 1-acid glycoprotein reduce the unbound metabolic clearance of disopyramide in patients with renal impairment?

The pharmacokinetics of disopyramide was studied in 15 patients with renal dysfunction (4 with pyelonephritis, 7 with glomerular nephritis and 4 with interstitial nephritis). The elimination rate constant of unbound disopyramide was 0.094 h-1 and CLu/f (unbound clearance divided by bioavailability) was 245 ml/min. Both the unbound renal clearance (CLR) and CLu/f were highly correlated with the creatinine clearance (CLCR). The apparent unbound metabolic clearance in the patients was approximately two-fold lower than that previously reported in normal subjects. The estimated unbound metabolic clearance in the renal dysfunction patients showed a significant negative correlation with the alpha 1-acid glycoprotein (AAG) concentration and only a weak, non-significant correlation with CLCR. As AAG in the renal dysfunction subjects was increased in comparison with normal values, it is possible that AAG is a factor in the decrease in the apparent unbound metabolic clearance.

Adult↗
PubMed1999

An equation to predict the changes in peak left ventricular pressure in hypertrophic obstructive cardiomyopathy after treatment: application to the administration of disopyramide.

A theoretical equation was derived based on the time-varying elastance model to predict theoretically the relationship between the delay in the onset of left ventricular outflow obstruction and the reduction in peak left ventricular pressure (LVP) caused by treatment in hypertrophic obstructive cardiomyopathy (HOCM). ECG, LVP, and other hemodynamic parameters were measured during catheterization at a constant heart rate with atrial pacing in 16 patients with HOCM before and after intravenous administration of disopyramide (1 mg/kg). After disopyramide administration, the duration between the R wave of the ECG and the onset of obstruction (T1) was prolonged significantly (from 117 +/- 30 to 155 +/- 32 ms, P < 0.0001), and peak LVP was reduced significantly (from 222 +/- 42 to 177 +/- 39 mmHg, P < 0.0001). The relation between the prolongation of T1 and the percent reduction in peak LVP was predicted well by the theoretical equation (coefficient of determination R2 = 0.926). Our model simplifies the therapeutic strategy for reducing the left ventricular outflow pressure gradient in patients with HOCM, which is to delay the time of onset of obstruction by some methods.

Adult↗
PubMed1978

Atypical ventricular tachycardia as a manifestation of disopyramide toxicity.

An unusual ventricular tachyarrhythmia developed in a 57 year old woman with recurrent ventricular tachycardia and toxic disopyramide plasma concentrations. The rhythm was similar to the patient's previous ventricular tachycardia, but the rate was slower and the QRS complex was markedly widened, mimicking the electrocardiographic changes associated with electrolyte abnormalities. Disopyramide, which has electrophysiologic properties similar to those of quinidine, probably caused the arrhythmia and should be added to the list of drugs associated with atypical ventricular tachycardia.

Administration, Oral↗
PubMed1979

Disopyramide-induced ventricular fibrillation.

Three cases are described with documented ventricular fibrillation shortly after the patients received disopyramide in moderate dosage. Electrocardiograms showed markedly prolonged Q-T intervals in two patients and a prominent U wave with a prolonged Q-U interval in one patient, but no change in QRS width. Disopyramide-induced ventricular fibrillation appears to be similar to that caused by quinidine and is an indication to discontinue the drug.

Administration, Oral↗