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 631 records · Page 35Linked to original sources
PubMed1997

Serum alpha 1-acid glycoprotein, sialic acid, and protein binding of disopyramide in normal subjects and cardiac patients.

AIM: To study influence of congestive heart failure (CHF) and acute myocardial infarction (AMI) on alpha 1-acid glycoprotein (AGP) and sialic acid (SA) concentration, and binding of AGP to disopyramide (Dis). METHODS: Sera from 85 healthy subjects, 6 patients with CHF, and 6 patients with AMI were determined by immunochemistry for AGP, by HPLC method for sialic acid (SA), and by ultrafiltration and HPLC for the free fraction of Dis. RESULTS: Serum AGP concentrations (g.L-1) were 0.74 +/- 0.16 (healthy), 1.18 +/- 0.40 (d 1, CHF) and 0.90 +/- 0.24 (d 14, CHF), 1.53 +/- 0.26 (d 5, AMI) and 1.08 (d 14, AMI). The free Dis were 1.76 +/- 0.62 (d 1) and 2.14 +/- 0.48 (d 14), in CHF patients, 1.66 +/- 0.52 (d 5) and 1.77 (d 14) in AMI patients. The changes of serum SA and AGP concentrations showed the same tendency. CONCLUSION: The free Dis in serum was affected by the change of AGP binding in CHF and AMI patients.

Adult↗
PubMed1975

[Clinical experimentation with intravenously administered disopyramide].

The intravenous injection of disopyramide (1.5 mg/kg) induces the return to sinus rhythm in about 60% of arrhythmias. When there exist perturbations of the cardiac rhythm, secondary to recent myocardial infarction, the percentage of success reaches 70%. The drug induces the disappearance of the extrasystoles in 80% of the cases, whatever the nature of the underlying cardiopathy. Although the secondary effects of the drug are slight, it is advisable to administer the substance in a slow intravenous injection (5 minutes), while controlling the arterial pressure and the E.C.G.

Adult↗
PubMed2000

Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of disopyramide enantiomers in humans.

To identify which cytochrome P-450 (CYP) isoform(s) are involved in the major pathway of disopyramide (DP) enantiomers metabolism in humans, the in vitro formation of mono-N-desalkyldisopyramide from each DP enantiomer was studied with human liver microsomes and nine recombinant human CYPs. Substrate inhibition showed that SKF 525A and troleandomycin potently suppressed the metabolism of both DP enantiomers with IC50 values for R(-)- and S(+)-DP of <7.3 and <18.9 microM, respectively. In contrast, only weak inhibitory effects (i.e., IC50 > 100 microM) were observed for five other representative CYP isoform substrates [i.e., phenacetin (CYP1A1/2), sparteine (CYP2D6), tolbutamide (CYP2C9), S-mephenytoin (CYP2C19), and p-nitrophenol (CYP2E1)]. Significant correlations (P <.01, r = 0.91) were found between the activities of 11 different human liver microsomes for mono-N-dealkylation of both DP enantiomers and that of 6beta-hydroxylation of testosterone. Conversely, no significant correlations were observed between the catalytic activities for DP enantiomers and those for the O-deethylation of phenacetin, 2-hydroxylation of desipramine, hydroxylation of tolbutamide, and 4'-hydroxylation of S-mephenytoin. Further evidence for involvement of CYP3A P450s was revealed by an anti-human CYP3A serum that inhibited the mono-N-dealkylation of both DP enantiomers and 6beta-hydroxylation of testosterone almost completely (i.e., >90%), whereas it only weakly inhibited (i.e., <15%) CYP1A1/2- or 2C19-mediated reactions. Finally, the recombinant human CYP3A3 and 3A4 showed much greater catalytic activities than seven other isoforms examined (i.e., CYP1A2, 2A6, 2B6, 2C9, 2D6, 2E1, and 3A5) for both DP enantiomers. In conclusion, the metabolism of both DP enantiomers in humans would primarily be catalyzed by CYP3A4, implying that DP may have an interaction potential with other CYP3A substrates and/or inhibitors.

Aged↗
PubMedDate not supplied

Torsades de pointes due to drug interaction between disopyramide and clarithromycin.

Torsades de pointes (TdP) is polymorphic ventricular tachycardia occurring in the setting of a prolonged cardiac repolarization. Drug interactions between macrolide antibiotics such as erythomycin and pharmacologic agents that prolong the QT interval have been known to cause TdP. However, clarithromycin is thought to be less frequently associated with drug induced TdP, because it inactivates hepatic cytochrome P-450 to a lesser extent than erythromycin. We describe a case of TdP caused by a drug interaction in a 76-year-old woman taking long-term disopyramide after she was given clarithromycin concomitantly for chronic bronchitis.

Aged↗
PubMed1979

[Antiarrhythmic action of disopyramide: a study of plasma levels].

The action of dysopyramide was studied in 13 patients, 11 with ventricular and 2 with supraventricular arrhythmias. The drug was given parenterally at first and then by mouth. The patients were monitored with an arrhythmia counter and the plasma levels of disopyramide measured throughout the treatment period. The plasma level was stable at about 4 micrograms/ml during the different phases. Toxic levels of 10 microgram/ml were observed in 1 patient in renal failure. The antiarrhythmic action was very effective (70% success), especially on the ventricular arrhythmias. Two of the four patients who failed to respond to treatment had low, non-therapeutic plasma levels. The dosage should be adapted with respect to the patient's weight and renal function.

Administration, Oral↗
PubMed2001

Disopyramide: interactions with marcolide antibiotics.

Cases of severe cardiac arrhythmia and major hypoglycaemia have occurred in patients receiving disopyramide simultaneously with some macrolide antibiotics, especially erythromycin and clarithromycin.

Anti-Arrhythmia Agents↗
PubMed2001

Population pharmacokinetics, protein binding and antiarrhythmic effects of disopyramide enantiomers in arrhythmic patients.

Disopyramide (DP) is widely used as an antiarrhythmic agent. The antiarrhythmic effects of its enantiomers differ from each other and its metabolism and protein binding are also stereoselective. Population pharmacokinetic parameters of DP racemate, enantiomers (S(+)-DP, R(-)-DP), and their unbound concentrations (uDP, S(+)-uDP and R(-)-uDP) were analyzed using the nonlinear mixed effect model (NONMEM) program. Data were available from 108 points of 33 arrhythmic patients on maintenance therapy with DP racemate. We evaluated the factors to which pharmacokinetic parameters are attributed and the relationships between each serum concentration and the antiarrhythmic effect. A one-compartment model was fitted to the data using NONMEM. For DP, S(+)-DP and R(-)-DP, elimination rate constants (kes) were estimated as 0.0648, 0.0663 and 0.0691/h, respectively and the mean apparent volume of distribution (Vd/F) were estimated as 63.2, 54.1 and 71.6 l, respectively. Using the ke and Vd/F values estimated by NONMEM, time-concentration curves were well fitted to the observed data. Unbound fractions of both DP enantiomers showed nonlinearity and the binding ratio of S(+)-DP was 0.84 +/- 0.07, which was higher than that of R(-)-DP [0.70 +/- 0.11 (p < 0.01)]. Unbound fractions of both DP enantiomers correlated with alpha1-acid glycoprotein (AGP) (p < 0.01). On the other hand, using NONMEM, a significant proportion of the variability of Vd/F could be attributed only to AGP (p < 0.001). NONMEM was able to clarify the pharmacokinetic features in the protein binding of DP. Individual steady state concentrations were estimated by NONMEM using the Bayesian method. The average unbound concentrations of all nine responders were higher than those of the four non-responders, even though this difference was not significant. Unbound concentrations may reflect drug concentrations in the tissue, which suggests that these concentrations may indicate an antiarrhythmic effect rather than the total concentration.

Adolescent↗
PubMed1976

Effects of disopyramide phosphate on ventricular arrhythmias in experimental myocardial infarction.

A myocardial infarction model in which infarction is the result of an occluding thrombus was used to evaluate the effectiveness of disopyramide phosphate (DP) in abolishing postinfarction ventricular arrhythmis. Two types of ventricular arrhythmias were observed, rapid multifocal arrhythmias. and slow unifocal rhythms. DP, in doses of 5 mg/kg, were effective against slow ventricular tachycardia. The time course of action varied with the type of rhythm present. Conversion of the slow ventricular tachycardia usually occurred within a minute whereas abolition of the rapid ventricular tachycardia took 5 to 10 minutes. Effective arrhythmia control could be maintained by a bolus dose (3 mg/kg) followed by a constant infusion at a rate of 0.2 mg/kg/min. DP had minimal effects on arterial blood pressure at antiarrhythmic doses. The drug had significant hypotensive effects if infused at rates greater than 2 mg/kg/min. However, the hypotensive effect was always transient at doses of 5 mg/kg or less. DP produced significant changes in the lead II electrocardiogram. At doses of 5 mg/kg, the drug significantly increased the P-R and Q-Tc intervals and increased the QRS duration. The drug slowed conduction through all parts of the conducting system to approximately the same degree with perhaps a slightly greater slowing through the atrioventricular node. However, the changes observed were never more than 20%

Animals↗
PubMed1991

Stereoselective disposition and metabolism of disopyramide in pediatric patients.

Pharmacokinetics of disopyramide (DP) enantiomers was studied in six pediatric patients, 5 to 12 years old, with arrhythmias after i.v. and p.o. administrations of racemic DP. The enantiomers of DP and its active metabolite, mono-N-dealkyldisopyramide, in plasma and urine were determined using a chiral, high-performance liquid chromatography. Plasma protein binding of DP was measured by ultrafiltration. Because the protein binding of DP was not only concentration-dependent but also stereoselective (i.e., S-DP binds to protein more extensively than R-DP), unbound pharmacokinetic parameters were used for evaluating the kinetic behaviors of DP enantiomers. The pediatric age patients had the mean (+/- S.D.) systemic clearance of 15.0 +/- 3.8 and 12.7 +/- 3.9 ml/min/kg for unbound S- and R-DP, respectively, which were not only stereoselectively different (P less than .05) but also at least about twice greater than the reported normal adult values. The mean postinfusion elimination half-life values for unbound S- and R-DP (2.7 +/- 0.5 and 2.8 +/- 0.4 hr, respectively) in pediatric patients were shorter than those reported from normal adults (approximately equal to 4 to 5 hr). The mean nonrenal (i.e., hepatic) clearance for unbound S- and R-DP (11.1 +/- 4.1 and 8.1 +/- 3.9 ml/min/kg, respectively) were also stereoselectively different (P less than .01) and accounted for approximately equal to 70% of the unbound systemic clearance of the respective enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Mechanographic assessment of disopyramide in postinfarction patients.

The inotropic effect of a per os single dose of 200 mg disopyramide phosphate was studied in 25 patients during the second week after acute myocardial infarction with no signs of heart failure. Systolic time intervals and the indices derived from the uncalibrated differentiated carotidogram and apexcardiogram were used to assess changes in cardiac performance. The results were as follows: a) Reduction by 3.2% of the haemodynamic ratio LVET/PEP. b) Reduction by 20.1% of the maximal relative upstroke velocity in the differentiated carotidogram (B/S2) p less than 0.05). c) Decrease by 13.1% of the ratio, total amplitude/dicrotic deflection (T/S2) in the same tracing (p less than 0.05). d) Decrease by 2.8% of the ratio, early systolic wave/early diastolic complex wave (b/ef) in the differentiated apexcardiogram. e) Increase by 3.2% of the ratio early diastolic complex total amplitude (ef/ZN) in the previous tracing. The above changes were indicative of a slight negative inotropic effect of the drug.

Administration, Oral↗
PubMed1991

Human pharmacokinetics and metabolism of disopyramide enantiomers.

The objective of the present study was to investigate human pharmacokinetics and metabolism of disopyramide (DP) enantiomers. Six healthy male volunteers entered the study. They were given, separately and via oral route, as repeated doses for 5 days, R(-) DP and S(+) DP at a dose of 100 mg twice daily. Unbound fractions of DP and metabolite (MND) enantiomers were obtained on each plasma sample, i.e. ex vivo, using ultrafiltration. Pharmacokinetic parameters of DP enantiomers based on total plasma concentrations were not significantly different. On the other hand, unbound pharmacokinetic parameters displayed marked stereoselectivity. The mean unbound clearance of R(-) DP and S(+) DP were 8.59 and 14.9 ml/min/kg, respectively (p = 0.003). The mean unbound renal clearance of R(-) DP and S(+) DP were 6.26 and 8.75 ml/min/kg, respectively (p = 0.025). The non renal clearance of R(-) DP and S(+) DP averaged 2.32 and 6.19 ml/min/kg, respectively (p = 0.002). The mean unbound volume of distribution of R(-) and S(+) DP were 225 and 381 liters, respectively (p = 0.023). The half-life of R(-) DP and S(+) DP averaged 4.17 and 3.91 hr, respectively (p = 0.21). The unbound fraction at steady-state of R(-) DP and S(+) DP averaged 12.5 and 7.5%, respectively (p = 0.002). In vitro binding experiments, performed for each subject, allowed to indicate that the stereoselective plasma binding was due to a stereoselective affinity, the binding capacity of both enantiomers being the same. Pharmacokinetic data emphasized the influence of stereoselectivity in the human disposition of DP enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Pharmacological analysis of drug interactions of disopyramide and its congeners with peripheral muscarinic acetylcholine receptors].

The interactions of the antiarrhythmic agents, disopyramide (D) and its congeners, pirmenol (Pr) and pentisomide (Pt), with peripheral muscarinic receptors (m-AchR) were investigated using binding and functional assays. D, Pr and Pt inhibited the specific binding of [3H]-N-methyl scopolamine ([3H]-NMS) to membrane fractions prepared from guinea pig left atria (LA), submandibular glands (SG) and urinary bladders (UB) in a concentration-dependent manner. Computer-assisted analysis showed that the displacement curves with D obtained from LA and UB were shallow and best fitted by a two-site model, whereas D interacted with a single class of binding sites in SG. Kinetic experiments measuring [3H]-NMS dissociation revealed the existence of allosteric interaction of D with m-AChR, and it might be responsible for the low affinity components of the displacement curves in LA and UB. The pKi values for D in high-affinity receptor sites in LA and UB (pKH) were very close to the pKi for D obtained in SG, and corresponded well to the pA2 values of around 6.0 for antagonism against the carbachol-induced mechanical responses of LA and UB. Pt interacted with m-AChR with qualitatively very similar fashion to that of D, but its potency was very weak (1/10 of D). Pr interacted with a single class of binding sites in LA and SG with pKi of 6.02 and 5.18, respectively, indicating that the affinity of Pr to glandular m-AChR (M3) was 7 fold lower than that to cardiac one (M2). The displacement curve with Pr in UB was best fitted by a two-site model with pKH of 5.93 and pKL of 5.20. The pA2 for Pr in LA and UB were 6.47 and 5.55, respectively, suggesting the existence of a mixed population of M2 and M3 in UB and the contribution of M3 to its contractile response. It is concluded that Pr is able to distinguish M2 from M3, and that D and Pt have almost similar affinity to both subtypes of m-AChR. Pr was less potent than D in interaction with M3.

Animals↗
PubMedDate not supplied

Pharmacokinetics of disopyramide in the dog. Importance of mono-N-dealkylated metabolite kinetics in assessing pharmacokinetic modeling of the parent drug.

The antiarrhythmic drug disopyramide (DP) is metabolized to the mono-N-dealkylated compound (MND) and to the pyrrolidone derivative (PYR). This study examines the detailed pharmacokinetic characteristics of DP and MND when given simultaneously or separately to dogs. DP and MND were both relatively well absorbed and showed similar pharmacokinetic characteristics. However, the amount of PYR relative to MND as judged by the area under the plasma concentration-time curves (AUC) following oral or iv administration was much greater with DP than with MND. These findings were also supported by the urinary excretion values where the PYR/MND ratio with DP was much greater than with the MND administration. For an explanation of this phenomenon, plasma concentration-time curves for DP, MND, and PYR were simultaneously analyzed assuming various pharmacokinetic models. The plasma levels of these compounds were best described when nonlinear kinetics were assumed for conversion of MND to PYR.

Absorption↗
PubMed1989

[Efficacy of disopyramide in the treatment of atrial flutter with overdrive pacing].

Thirty patients with long-standing (mean 30 days) type I atrial flutter (AF) were treated with overdrive atrial pacing. To evaluate the effect of pretreatment with disopyramide (DISO), the study population was divided into 3 groups of 10 patients each: no therapy (Group A); intravenous DISO (maximum dose 250 mg in 1 hour) (Group B), oral DISO (400 mg/day for 4 days) (Group C). The mean cycle length of AF was 215 +/- 24 ms in Group A, 222 +/- 28 in B and 224 +/- 11 in C (NS). After DISO, AF cycle length increased to 287 +/- 24 in Group B (p less than 0.001) and to 264 +/- 29 in C (p less than 0.001). Overdrive pacing was performed from a maximum of 3 atrial sites up to the shortest paced cycle of 150 ms. Reversion to sinus rhythm (SR) occurred in 20% of patients in Group A, 70% in B and 50% in C. In all these cases SR was obtained with paced cycle length that was 70-90% of the baseline cycle length. Pacing was performed from a mean number of 2.1 sites per patient in Group A, 1.2 in B and 2.0 in C. Atrial fibrillation occurred in 7, 3 and 4 patients, respectively. Acceleration of atrial flutter to a faster form of AF occurred in 3, 3 and 4 patients, respectively. The administration of DISO prior to overdrive atrial pacing improves the rate of conversion to SR and allows an easier stimulation protocol with a lower incidence of pacing-induced atrial fibrillation. The administration of DISO is beneficial when overdrive atrial pacing is performed for the treatment of long standing AF in patients with organic heart disease.

Aged↗
PubMed1987

In vitro study of gastrointestinal diffusion system using disopyramide phosphate.

Gastrointestinal Diffusion System (GDS) provides release of a drug by means of a controlled source of diffusion energy. The unit can possibly be used for all soluble agents in which solubility is independent of the pH of the gastrointestinal contents as is the case with disopyramide phosphate. The GDS consists of a soluble tablet-core, surrounded by a cellulose acetate film containing a soluble pore-creating agent. When the pore-creating agent is removed from the coating film, the cellulose acetate membrane which remains is of a porous nature, which controls the diffusion rate of the drug. The release rate of the drug can be varied by changing the composition and mass of the membrane. The resultant system in vitro provides the zero-order drug delivery due to the appropriate selection of manufacturing parameters.

Delayed-Action Preparations↗
PubMed1978

The anti-arrhythmic efficacy of perhexiline maleate, disopyramide and mexiletine in ventricular ectopic activity.

The anti-arrhythmic efficacy of perhexiline maleate, disopyramide and mexiletine has been evaluated in 27 patients with chronic ischaemic heart disease who exhibited frequent ventricular ectopic beats (i.e. greater than or equal to 8/h). Holter tape recordings were made during normal working hours before, during and after the sequential administration of the three drugs. Each drug was administered to each patient for a 2-month period. The drug had to be discontinued in 4 cases because of side-effects. A significant reduction (P less than 0,001) in ectopic beat frequency occurred with all three drugs. No significant difference in anti-arrhythmic potency could be demonstrated between the drugs.

Adult↗
PubMed1986

Myocardial and ventricular mechanics as influenced by disopyramide.

The effects of disopyramide (D) on the mechanics of isolated myocardium as well as on the whole ventricle were examined in the rat model. Moreover bipolar leads of the apex and an area at the base of the left ventricle were set up to get indications for changes in the spread of excitation. D in concentrations of 10(-8) to 10(-4) mol/l did not affect the diastolic elastic properties of isolated myocardium. Isometric contraction amplitude was nearly unaltered, while rate of isometric contraction and relaxation were slightly increased. In the whole ventricle in situ D (2 to 10 mg/kg b.w. administered i.v.) induced a dose-dependent decrease in left ventricular isovolumetric peak pressure (16%), max.pos. dP/dt (40%) and max.neg. dP/dt (30%; for highest doses respectively), while time to peak pressure and relaxation time 90% were prolonged. Therapeutic dose of D (2 mg/kg b.w.i.v.) induced no decrease in essential systolic parameters of the whole ventricle under auxotonic conditions. Left ventricular pressure, dP/dt max.pos. and neg., left ventricular end-diastolic pressure and cardiac output were nearly unaltered. Heart rate showed a tendency to decrease, while total time of contraction and left ventricular ejection time increased. Higher doses of D led to marked cardiac depressant effects. The time interval between the excitation of the apex and an area at the base of the heart was increased. It was concluded that the negative dromotropic effect of D and thereby an altered pattern of left ventricular contraction are essential components in the elimination of the pressure gradient between left ventricle and aorta, observed in patients with muscular subaortic stenosis, and are presumably involved in the cardiac depressant effect of the drug in over-therapeutic doses.

Animals↗
PubMedDate not supplied

[Pharmacodynamics and pharmacokinetics of disopyramide phosphate].

Based on pharmacodynamic and pharmacokinetic studies in 42 patients with paroxysmal and extrasystolic abnormalities of the rhythm it was established that disopyramide phosphate (ritmilen) is an effective antiarrhythmic agent for atrial fibrillation paroxysms. The drug exerts negative, chronotropic, dromotropic and inotropic effects, especially upon intravenous injections for removal of atrial fibrillatin paroxysms. Ritmilen moderately reduces the blood pressure. When used for removal of atrial fibrillation paroxysms ritmilen is effective in doses of 1.2-1.7 mg/kg intravenously and in doses of 2.5-3.8 mg/kg per os. In patients with chronic ventricular premature heart beat the single effective drug doses amount to 0.61-1.7 mg/kg. After oral use the ritmilen concentration in blood plasma is lower than after intravenous use in adequate doses. No relationship has been found between the drug antiarrhythmic effect and blood plasma concentration.

Adult↗