Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Disopyramide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1984

Disopyramide pharmacokinetics and bioavailability following the simultaneous administration of disopyramide and 14C-disopyramide.

The pharmacokinetics and bioavailability of total (bound plus unbound) and unbound disopyramide were compared following the simultaneous administration of an oral dose of disopyramide and an intravenous dose of 14C-disopyramide in five normal volunteers and in 11 patients with congestive heart failure. The binding of disopyramide varied between 60 and 92% in patients and between 81 and 88% in normal subjects at postequilibrium drug concentrations of 10(-7) M. The binding of disopyramide to serum protein was concentration-dependent in all study subjects at serum concentrations achieved following drug administration. The association constant for the first binding site in serum from normal subjects and patients averaged 8.7 X 10(5) M-1 and 4.4 X 10(5) M-1, respectively (p less than 0.05). The unbound clearance of disopyramide averaged 277 ml/min and 209 ml/min in normal subjects and in patients (p less than 0.05). When normalized for body weight, the unbound clearance between patients and normal subjects was not significantly different. The elimination half-life of unbound concentrations in normal subjects and in patients averaged 4.9 and 6.1 h, respectively (p less than 0.05). The clearance and elimination half-life of total disopyramide was the same in both groups. Although the bioavailability of disopyramide averaged 0.85 in both groups, it was more variable in patients owing to the variability in the fraction of the dose absorbed. The unbound renal clearance and volume of distribution at steady state of disopyramide was related to cardiac index. The ratio of elimination half-lives of total and unbound disopyramide was related to the extent of serum protein binding.

Adult↗
PubMed1995

Relationship between the therapeutic effects or side-effects and the serum disopyramide or mono-N-dealkylated disopyramide concentration after repeated oral administration of disopyramide to arrhythmic patients.

After we had developed a method to determine simultaneously the blood concentrations of disopyramide (DP) and its metabolite mono-N-dealkylated disopyramide (MND) by high-performance liquid chromatography, DP was administered repeatedly to arrhythmic patients in order to examine the relationship between the serum DP or MND concentration and the therapeutic effects or side-effects. To 79 arrhythmic patients (57 patients with ventricular premature contraction, 13 with supraventricular arrhythmia and 9 with atrial fibrillation), DP was administered repeatedly at an initial oral dose of 200 to 400 mg/day. Of the 61 patients which were possible to evaluate after reaching a steady state, 32 were evaluated as effective and 29 as non-effective, the effective rate being 52.5%; the mean blood DP concentration (+/- S.D.) was 2.14 +/- 0.65 and 1.74 +/- 0.62 micrograms/ml, respectively, with a significant difference between the two groups (p +/- 0.05). At the final dose, 40 patients were evaluated as effective and 18 as non-effective, the effective rate being 69.0%; the mean blood DP concentration was 2.03 +/- 0.67 and 2.09 +/- 0.68 micrograms/ml, respectively, with no significant difference between the two groups. Among 42 patients with premature contraction, 26 were evaluated as effective and 16 as non-effective, the effective rate being 62%; the mean blood DP concentration was 2.01 +/- 0.62 and 2.20 +/- 0.70 micrograms/ml respectively, with no significant difference between the two groups. The incidence of side-effects was 17.7%, and there were no significant differences in blood DP or MND concentrations between the groups with and without side-effects. A blood DP concentration more than 2 micrograms/ml may be required to achieve the therapeutic effect of DP administered repeatedly.

Adult↗
PubMed1981

Plasma concentrations and protein binding of disopyramide and mono-N-dealkyldisopyramide during chronic oral disopyramide therapy.

1 The plasma levels of disopyramide and mono-N-dealkyldisopyramide were measured from 118 patients, and the protein binding of both drugs from 50 patients during chronic oral disopyramide therapy. 2 No significant correlation was seen between the daily dose of disopyramide and the achieved plasma drug concentration. 3 The concentration of mono-N-dealkyldisopyramide in the plasma was about one third of that of disopyramide in patients with normal renal function. 4 The mean plasma levels of disopyramide and mono-N-dealkyldisopyramide were high in patients with renal impairment. In patients with simultaneous therapy with enzyme inducing drugs the mean levels of disopyramide were low and those of mono-N-dealkyldisopyramide high. 5 In patients with effective treatment of ventricular arrhythmias the levels of disopyramide were significantly higher than in those with ineffective treatment; the difference was not significant in supraventricular arrhythmias. Patients with side-effects had slightly though not significantly higher disopyramide levels than patients without side-effects; mono-N-dealkyldisopyramide concentrations were identical. 6 The average protein binding of disopyramide was 82%, and that of mono-N-dealkyldisopyramide 22-35%. Although a concentration dependent binding of disopyramide was seen within an individual, the average protein binding did not vary significantly at different concentrations of all samples analyzed. The protein binding was not altered in renal insufficiency, but was slightly decreased by high concentrations of mono-N-dealkyldisopyramide.

Aged↗
PubMed1982

The pharmacokinetics of disopyramide and mono-N-dealkyl-disopyramide in humans.

The pharmacokinetics of disopyramide and its metabolite mono-N-dealkyl-disopyramide (MND) were studied after a single oral and intramuscular dose and at steady state in healthy volunteers, after an intravenous dose in post-surgery patients, and after a single oral dose in two patients with renal insufficiency. After an oral dose in healthy volunteers the plasma elimination half-life of total disopyramide was 8.65 +/- 1.37 h, and that of the non protein-bound disopyramide, 4.74 +/- 1.20 h. The protein binding of disopyramide varied from 0.58 to nearly 1.0, and was concentration dependent. All subjects had detectable amounts of MND in plasma. Its elimination half-life was 12.9 +/- 6.43 h. The ratio of MND to disopyramide was 0.23 +/- 0.09 in plasma and 0.46 +/- 0.11 in urine. There was a close correlation (r = 0.868) between the renal clearances of free disopyramide and creatinine. The renal clearances of disopyramide (both free and total), MND, and creatinine varied with time; this resembled variation in the urine flow. The kinetics of one dose at steady state did not differ markedly from that of a single dose. The elimination half-lives of total disopyramide varied from 4.4 to 17.1 in post-surgery patients, and those of the renal patients were 10.6 and 8.7 h.

Administration, Oral↗
PubMed1997

Disopyramide concentrations in human plasma and saliva: comparison of disopyramide concentrations in saliva and plasma unbound concentrations.

OBJECTIVE: This study was performed to investigate whether it is possible to use saliva instead of blood usually used for therapeutic drug monitoring (TDM) of disopyramide. METHODS: Six healthy male volunteers ingested 200 mg of disopyramide base, and the disopyramide concentrations in saliva and plasma (total and unbound) were determined by the HPLC. RESULTS: Disopyramide concentration-time profiles for the saliva were nearly equal to those for the plasma unbound concentrations. A large variation for absorption time of the drug was observed among the subjects. Disopyramide concentrations (Cs) in saliva did not correlated well with plasma total concentrations (Cp), r = 0.799, but did well with unbound concentrations (Cpu), r = 0.969, for the 3-12 h period on the elimination phase. The mean ratio of disopyramide concentrations in the saliva against the plasma unbound concentrations was almost constant (1.02(0.10), CV = 9.7%) for the period. The pharmacokinetic parameters (tmax, t1/2, AUC, AUMC and MRT values) for disopyramide calculated from the saliva data were nearly equal to those from the unbound data. CONCLUSION: Disopyramide concentrations in saliva correlated well with plasma unbound concentrations on the elimination phase.

Adult↗
PubMed1987

Transfer from immediate-release disopyramide to controlled-release disopyramide.

Simulation of serum disopyramide concentrations during transfer from steady-state immediate-release (IR) disopyramide to a sustained-release disopyramide preparation was performed based on pharmacokinetic parameters obtained from IR disopyramide and serum concentrations measured following an initial dose of controlled-release (CR) disopyramide phosphate. Based on the results of simulation, a typical patient with good cardiac, renal, and hepatic function can be transferred from a q 6 h IR disopyramide to an equivalent daily dose of controlled-release disopyramide administered q 12 h beginning at 6 hours after the final IR disopyramide dose.

Anti-Arrhythmia Agents↗
PubMed1987

Effects of disopyramide on detrusor muscle contraction: in vitro experiment and report of 3 cases with disopyramide-induced urinary retention.

Three cases of disopyramide-induced urinary retention were reported and effects of disopyramide on agonist-induced contraction of detrusor muscle were studied in vitro. Muscle strips were obtained from rabbit bladder body and changes in isometric contraction of the strips were monitored. Acetylcholine, prostaglandin F2-alpha, potassium chloride, barium chloride, adenosine triphosphate and Ca2+ were used as agonists for detrusor muscle contraction. Disopyramide relaxed the contraction elicited by acetylcholine in normal Krebs solution, but exhibited no relaxing effect on contractions induced by prostaglandin F2-alpha, potassium chloride, barium chloride and adenosine triphosphate. In Ca2+-free Krebs solution, basal tension of the strips declined and spontaneous contractile activity was eliminated. Replenishment of 3 mM Ca2+ induced a slow contraction and redevelopment of spontaneous contraction of the strips. Pretreatment of the strips with disopyramide had no inhibitory effect on the Ca2+-induced contraction or on the spontaneous contractile activity in Ca2+-free solution. In normal Krebs solution, acetylcholine (10(-9)-10(-2)M) caused dose-dependent contractions of the detrusor muscle strips. Pretreatment of the strips with disopyramide (10(-5)-10(-3)M) dose-dependently inhibited the acetylcholine-induced contraction in a competitive way. The inhibitory effect of disopyramide on acetylcholine-induced contraction was less potent than that of atropine. We conclude that disopyramide may inhibit detrusor contractile activity mostly by its anticholinergic effect, resulting clinically in micturition disturbance.

Acetylcholine↗
PubMed1992

Comparative class 1 electrophysiologic and anticholinergic effects of disopyramide and its main metabolite (mono-N-dealkylated disopyramide) in healthy humans.

During steady-state treatment with disopyramide, its main and active metabolite, mono-N-dealkylated disopyramide, was reported to reach concentrations that were equal to or higher than the parent drug in 25% of 70 evaluated patients. This metabolite has been found to have a more pronounced anticholinergic action than the parent drug on in vitro evaluation, but neither its anticholinergic nor its direct electrophysiologic effects on the human heart have been properly assessed. We therefore compared the acute electrophysiologic and anticholinergic effects (the standard being atropine, 0.04 mg/kg) of disopyramide and its main metabolite, given 2 mg/kg body weight intravenously to 10 healthy individuals in a double-blind, randomized, crossover design. The anticholinergic effect of these substances on sinus and atrioventricular node function was unexpectedly found to be of similar magnitude and more pronounced than previously thought (at least one-third the effects of the atropine dose). The class 1 electrophysiologic effects were as follows: intra-atrial and His-Purkinje conduction (the PA and the HV interval, respectively) was prolonged 33% (95% CI: 18-47%) and 27% (21-32%) by disopyramide, and 15% (10-19%) and 13% (10-17%), respectively, by the metabolite. Disopyramide also prolonged the QRS, JT, and QT intervals by 15% (9-21%), 10% (8-13%), and 10% (7-12%), respectively. The metabolite caused a 9% (7-12%) prolongation of the QRS interval (significantly less than disopyramide), but shortened repolarization (as reflected by the JT interval) by -7% (-2 to -11%; p < 0.01), which is similar to the acute effects of lidocaine 2 mg/kg body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

The anticholinergic side effects of disopyramide and controlled-release disopyramide.

Until now, the potential antiarrhythmic benefits of disopyramide have been restricted by anticholinergic side effects. These side effects have included xerostomia (dry mouth, nose or eyes), abdominal discomfort, nausea, constipation and, most importantly, urinary hesitancy and retention. A sustained-release form of pyridostigmine, an acetyl-cholinesterase inhibitor, has been shown to a) prevent the anticholinergic side effects of disopyramide when used prophylactically and b) to eliminate or attenuate these symptoms if they are already present. Pyridostigmine has no measurable effect on disopyramide's antiarrhythmic properties. This represents a beneficial new drug interaction which will improve tolerance of disopyramide and increase patient compliance with disopyramide-containing regimens.

Delayed-Action Preparations↗
PubMed1991

Simplified, rapid and inexpensive extraction procedure for a high-performance liquid chromatographic method for determination of disopyramide and its main metabolite mono-N-dealkylated disopyramide in serum.

A simplified, rapid and inexpensive extraction procedure for the determination of the antiarrhythmic drug disopyramide and its main metabolite mono-N-desalkylated disopyramide in serum by high-performance liquid chromatography has been developed. The analysis uses ultraviolet detection at 254 nm, and a 5 micron reversed-phase column with a mobile phase of water-triethylamine-acetonitrile-PIC-B8 reagent. Serum extraction is performed with dichloromethane and 1 M sodium hydroxide. p-Chlorodisopyramide is used as internal standard. Recovery rates were 94.5% (S.D. 5.7%) for disopyramide, 96.8% (S.D. 2.2%) for mono-N-desalkylated disopyramide and 97.9% (S.D. 2.8%) for the internal standard.

Chromatography, High Pressure Liquid↗
PubMed1991

[Delayed-action disopyramide in the treatment of hyperkinetic ventricular arrhythmia. A randomized clinical comparative study vs immediate-action disopyramide].

The authors report the results of an open randomized study to compare the efficacy of oral slow-release and immediate-release disopyramide, in the treatment of patients with chronic stable ventricular arrhythmias, evaluated with two Holter recordings. Twelve patients, selected after positive acute intravenous test, had been randomly assigned to slow-release (500 mg/day) and immediate-release (400 mg/day) disopyramide. Ten days later, a Holter recording was performed and then all patients were treated with slow-release disopyramide (500 mg/day); After one month drug efficacy has been evaluated by Holter recording. Total ectopic beats and arrhythmic Lown modified score were the end points. Immediate-release disopyramide significantly reduced both total beats and arrhythmic score; the slow-release formulation did not modify total beats and reduced the arrhythmic score, but only at the first Holter control. One month later there was no significant difference in arrhythmic score either. Low plasma drug levels could explain these results in some patients.

Aged↗
PubMed1979

Induction of disopyramide N-dealkylation by phenobarbital and disopyramide in rat liver.

An in vitro assay for the determination of the activity of disopyramide-N-dealkylation was developed. This reaction was concluded to be catalyzed by the liver microsomal, cytochrome P-450 centered monooxygenase system. Phenobarbital enhanced the N-dealkylation of disopyramide four fold, and disopyramide itself 1.6 fold, whereas methylcholanthrene was without effect. Disopyramide also increased ethoxycoumarin deethylation 1.6 fold, and had a slight increasing effect on the activity of epoxide hydratase, but did not affect the activities of glutathione S-transferase or UDPglucuronosyltransferase.

Animals↗
PubMed1983

Determination of disopyramide and mono-N-desisopropyl-disopyramide in serum by gas-liquid chromatography with nitrogen-selective detection.

A rapid, reliable assay is described for the quantitation of disopyramide (DP) and its metabolite, mono-N-desisopropyl-disopyramide (MNDP), in serum using p-chloro-disopyramide as the internal standard and aqueous standards for calibration. The procedure involves extraction of the serum sample with diethyl ether, derivatization of MNDP with acetic anhydride, and gas-liquid chromatographic analysis with nitrogen-selective detection. The accuracy of the procedure is 97.8 +/- 10.3 (SD)% for DP over the concentration range, 0.25-10.00 micrograms/ml (n = 37), and 99.6 +/- 10.2 (SD)% for MNDP over the concentration range, 0.50-5.00 micrograms/ml (n = 18). The within-day coefficient of variation is less than 8% for DP and 12% for MNDP. The lower limit of quantitative sensitivity is 0.25 micrograms/ml for DP and 0.50 micrograms/ml for MNDP, and the lower limit of detection is 0.6 ng and 1.6 ng, respectively, for DP and MNDP. This assay has been used to determine the time-course of DP and MNDP and the protein binding of DP (without requiring an in vitro protein binding curve) in the serum obtained from patients and laboratory animals during DP administration.

Chromatography, Gas↗
PubMed1988

Direct enantiomeric resolution of disopyramide and its metabolite using chiral high-performance liquid chromatography. Application to stereoselective metabolism and pharmacokinetics of racemic disopyramide in man.

A method for the simultaneous determination of disopyramide and mono-N-desisopropyldisopyramide enantiomers extracted from human plasma and urine is presented. Separation and quantitation were carried out using two columns coupled in series, and UV detection at 254 nm. First, the racemates of the two compounds were separated using a reversed-phase column, and then the enantiomers were separated using a stereoselective column packed with human alpha 1-acid glycoprotein. The mobile phase was 8 mM phosphate buffer, pH 6.20-2-propanol (92:8, v/v). The coefficients of variation (%) for the plasma daily determination were 6.7% for R(-)- and S(+)-disopyramide at drug levels of 1.5 micrograms/ml, and 8.5% and 7.7% for R(-)- and S(+)-mono-N-desisopropyldisopyramide, respectively, at drug levels of 0.375 micrograms/ml. The method has allowed the study of stereoselective metabolism and pharmacokinetics of disopyramide after oral administration as a racemate.

Administration, Oral↗
PubMed1989

Disopyramide and N-monodesalkyl disopyramide in serum and breast milk.

Maternal serum and breast milk were obtained to determine the concentration of disopyramide (DP) and its metabolite N-monodesalkyl disopyramide (NMD) from a woman requiring antidysrhythmic drug therapy. Infant serum and urine were also obtained for drug concentrations. DP 450 mg tid resulted in peak maternal serum concentrations of 4.0 micrograms/mL and 2.2 micrograms/mL for DP and NMD, respectively. Breast milk concentrations averaged 1.06 and 6.24 times the serum levels for DP and NMD, respectively. No DP was measurable in the infant's serum except for cord blood, which contained 0.7 micrograms/mL DP, 26 percent of simultaneous maternal concentration, and 0.9 micrograms/mL NMD, which represented 43 percent of the maternal concentration. Infant urine collected over an eight-hour period contained 3.3 micrograms/mL of DP and 3.7 micrograms/mL of NMD.

Adult↗
PubMed1984

The efficacy of quinidine and disopyramide in the maintenance of sinus rhythm after electroconversion from atrial fibrillation. A double-blind study comparing quinidine, disopyramide and placebo.

In order to compare the relative efficacy of quinidine, disopyramide and a placebo in the maintenance of sinus rhythm after cardioversion from atrial fibrillation and in order to examine the incidence of side-effects, 82 patients with continuous atrial fibrillation (duration more than 1 month but less than 3 years) were randomized in a double-blind fashion to receive quinidine, disopyramide or placebo. Six months after cardioversion there was no significant difference between any of the three groups as regards the number of patients remaining in sinus rhythm. The greater distortion of the atrial architecture which occurs in patients with rheumatic mitral valve disease may explain the failure of these anti-arrhythmic agents to prolong the duration of sinus rhythm in this study, in which patients with valvular heart disease comprised 76% of the total group.

Adolescent↗
PubMed1989

Combined effect of disopyramide and bethanechol: use of bethanechol to prevent anticholinergic side effects of disopyramide without reduction of antiarrhythmic efficacy.

Because bethanechol chloride (B) relieves the anticholinergic side effects of disopyramide (D), we examined the combined effects of D and B on the heart and urinary bladder. B was confirmed to counteract dose dependently the effect of D on the dog bladder. In the ventricular muscle, the combined electrophysiological effects (D + B) were additive, with no reduction in the effect of D. With the control value set as 100%, the decrease in the maximum rate of depolarization with 5 X 10(-6) g/ml D (90 +/- 6%) was not affected by the same dose of B (D + B: 84 +/- 14%). Moreover, the effective refractory period (ERP) was larger with D + B (128 +/- 12%) than with either B (109 +/- 9%, p less than 0.01) or D (115 +/- 11%, p less than 0.05). In contrast, in the atrial muscle and AV and SA nodes, B had marked acetylcholine-like effects. These were completely suppressed by the addition of D except for the atrial ERP with the highest tested concentration of B (5 X 10(-6) g/ml). In the latter case, the prolongation of ERP was minimal (B + D: 105 +/- 14%) as compared with D alone (130 +/- 15%). Since the plasma concentration of B after oral administration of a clinical dose is expected to be on the order of 10(-7) g/ml, no practical effect is anticipated. We conclude that B can be expected to counteract urination disorders caused by D without reducing D's antiarrhythmic efficacy.

Anesthesia↗