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 73 records · Page 4Linked to original sources
PubMed1989

Hemodynamic and electrophysiologic effects of disopyramide enantiomers in a canine blood superfusion model.

The use of disopyramide is often limited because of adverse hemodynamic or electrophysiologic side effects. We compared the S(+) and R(-) enantiomers of disopyramide to the clinically used racemic mixture in a canine blood superfusion model. Eighteen support animals (group I) provided extracorporeal blood superfusion of isolated canine cardiac Purkinje fibers. Following administration of 2 mg/kg disopyramide intravenously (i.v.) [S(+), R(-), or racemic] hemodynamic and electrocardiographic parameters were temporally assessed in the support animals while simultaneous cellular electrophysiologic effects were recorded from the blood-superfused Purkinje fibers. An additional 13 animals (group II) underwent extended hemodynamic and pharmacokinetic analysis without the external atrioventricular (AV) shunt required for blood superfusion. Mean peak serum concentrations of racemic disopyramide and its enantiomers were similar (2.7 to 3.1 mg/L), but clearance was stereo-specific [half-life (t1/2) of 1.99 h for S(+) vs. 2.79 h for R(-) disopyramide]. Left ventricular (LV) function was impaired following drug administration, irrespective of optical rotation (cardiac output decreased by 20.8%, LV dP/dtmax decreased by 22.4%). Depression of phase 0 Vmax of the Purkinje fiber action potential was also nonstereo-dependent. S(+) disopyramide prolonged the QTC interval by 11.5% and increased terminal action potential duration (APD75) and effective refractory period (ERP) by 21.2 and 19.0%, respectively. R(-) disopyramide slightly increased the QTC interval (+2.3%) but decreased APD75 and ERP by 8.9 and 6.8%, respectively. The effect of racemic disopyramide on repolarization indexes was intermediate to that of its enantiomers. These data support nonstereodependent depression of both myocardial contractility and sodium channel conductance by disopyramide. Changes in APD and refractoriness were dependent on stereochemical configuration.

Animals↗
PubMedDate not supplied

Stereoselective pharmacokinetics of disopyramide enantiomers in man.

The plasma protein binding and pharmacokinetics of S(+)-disopyramide and R(-)-disopyramide following infusions of 100 mg were compared in five healthy human volunteers. The binding of S(+)-disopyramide was higher than that of R(-)-disopyramide at similar unbound concentrations in all subjects. The association constant characterizing the interaction between plasma protein and the S(+)- and R(-)-enantiomers was 17.1 X 10(5) M-1, and 7.68 X respectively. The unbound clearance and half-life of S(+)-disopyramide averaged 604 ml/min and 3.67 hr, respectively, and differed from that of R(-)-disopyramide, which averaged 401 ml/min and 4.62 hr, respectively. Both enantiomers appear to undergo active tubular secretion. The unbound renal clearance of the S(+)- and R(-)-enantiomers averaged 338 and 182 ml/min, respectively (p = 0.05). The unbound steady-state volume of distribution of S(+)- and R(-)-disopyramide averaged 172 and 141 liters, respectively (p = 0.14). The renal clearance of the mono-N-dealkylated metabolite of disopyramide following the administration of S(+)- and R(-)-disopyramide averaged 345 and 170 ml/min, respectively (p less than 0.05).

Blood Proteins↗
PubMedDate not supplied

Species-dependent binding of disopyramide enantiomers.

Serum protein binding of the basic enantiomers of disopyramide were studied in several animal species. (S)-(+)-Disopyramide was more highly bound than the (R)-(-)-enantiomer to serum protein in the man, gorilla, and pig. The reverse was true in cow serum, and in serum and albumin from sheep. Enantioselective differences in binding were due to differences in association constants. No enantioselective differences in binding were observed in serum protein from horse and goat, or in albumin from cow and pig. Disopyramide was highly bound to two sites on horse albumin. The association constant characterizing the binding of disopyramide to the first (major) site on horse albumin was 1.3 x 10(7) M-1. At predialysis concentrations of 10(-7) M, tris-(2-butoxyethyl)phosphate displaced disopyramide from sites on horse albumin and from sites on serum protein from the horse, man, gorilla, cow, and pig. At predialysis concentrations of 10(-5) M, warfarin and diazepam had no effect on disopyramide binding in these animal species. It is concluded that the enantioselective binding of disopyramide is species dependent, the site that is responsible for the moderate to high binding of disopyramide enantiomers is probably located on alpha 1-acid glycoprotein, and the sites that bind disopyramide in the horse are located on albumin and may be unique.

Animals↗
PubMed1982

Disopyramide concentrations in saliva.

The saliva and plasma concentrations of disopyramide and its main metabolite, mono-N-dealkyldisopyramide, and the protein binding of disopyramide were studied in ten healthy volunteers after a single oral 400-mg dose of disopyramide. Disopyramide had a concentration-dependent inhibitory effect on the salivary flow rate. The correlations between the salivary and total plasma concentrations of disopyramide (r = 0.774 linear, 0.890 exponential, p less than 0.0001), of the metabolite (r - 0.700, p less than 0.001), and between the salivary and free plasma concentrations of disopyramide (r = 0.785, p less than 0.001) were relatively good. The fraction of disopyramide not bound to plasma proteins varied from not measurable to 0.35, was concentration-dependent, and showed intersubject variation. The ratio of disopyramide concentrations in saliva and plasma (S/P ratio) varied from 0.08 to 1.51 and was highest when the salivary and plasma levels were high. No significant correlation existed between S/P ratio and salivary pH, and the correlation was poor (r = 0.546) between the measured salivary concentrations and those calculated theoretically. A wide interindividual variation was seen in all parameters measured. The salivary concentrations of disopyramide are unreliable for predicting the corresponding total or free plasma concentrations.

Adult↗
PubMed1987

Propafenone versus disopyramide: a double-blind randomized crossover trial in patients presenting chronic ventricular arrhythmias.

In vitro and in vivo electrophysiological studies have shown that propafenone could be classified as a class I antiarrhythmic agent. The aim of this study was to investigate the short-term antiarrhythmic efficacy and safety of propafenone in 10 patients compared to disopyramide in a double-blind randomized protocol. Included patients suffered from ventricular arrhythmias with at least 60 ventricular premature beats (VPB) per hour refractory to at least two other antiarrhythmic agents. At the end of the control period and of the two treatment periods during which patients received either propafenone (300 mg three times a day) or disopyramide (200 mg three times a day), clinical examination, Holter recordings, electrocardiogram, and clinical laboratory tests were performed. The PR interval and the QRS interval were significantly increased with propafenone, but not with disopyramide. The cQT interval was not significantly changed by either propafenone or disopyramide. Heart rate was decreased with propafenone (p less than 0.05) with no change in the diurnal/nocturnal circadian ratio variation. Heart rate was significantly decreased with disopyramide only during the day. Five of nine patients in the propafenone group and two of nine patients in the disopyramide group showed a reduction in ventricular premature beats greater than 80%. Total resolution of severe arrhythmias (repetitive events) was seen in 5 of 8 patients with propafenone; 2 of 8 with disopyramide. Adverse events, when they occurred, were mild (visual disturbances, epigastric discomfort, changes in taste perception, transient atrioventricular block with propafenone, and photophobia with disopyramide), and did not require reduction or discontinuation of study drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Clinical pharmacokinetics of controlled-release disopyramide in patients with cardiac arrhythmias.

UNLABELLED: The pharmacokinetics of the controlled-release preparation of disopyramide phosphate (Norpace CR, Searle Laboratories, Chicago, IL) were studied in ten patients with cardiac arrhythmias. Multiple-serum disopyramide concentrations were obtained after a 300-mg oral dose. Each patient then received chronic oral therapy with the controlled-release preparation (400 to 1000 mg/day) on an every-12-hour schedule. At steady state, disopyramide trough concentrations were obtained. Serum disopyramide concentrations were determined by high performance liquid chromatography. The regimen was well tolerated by all patients. The mean (+/- SD) time to maximum concentration, maximum concentration, and concentrations 11 and 24 hours after the initial dose were 5.5 +/- 1.3 hours and 2.8 +/- 0.8, 2.0 +/- 0.9, and 1.2 +/- 0.5 micrograms/mL, respectively. A low Cmax to trough concentration ratio of 1.35 +/- 0.26 was observed after the initial dose. Linear regression analysis of the serum disopyramide concentrations 11 hours after initial dose (trough) versus trough concentrations at steady state (dose adjusted) showed a strong correlation (r = 0.87, intercept = 0.03, and slope = 1.9). Regression analysis also showed a strong relationship between the area under the curve (AUC) from time 0 to 11 hours after the initial dose and the trough at steady state (r = 0.86). CONCLUSIONS: The controlled-release preparation of disopyramide, when administered every 12 hours in patients with cardiac arrhythmias, should produce low peaks to trough fluctuations. Because disopyramide concentrations after the initial dose correlate well with trough concentrations at steady state, these concentrations may provide a simple and convenient method for prospective monitoring of disopyramide therapy in patients receiving the controlled-release preparation.

Adult↗
PubMed1986

In vivo interaction of the enantiomers of disopyramide in human subjects.

Disopyramide, an antiarrhythmic agent, is marketed as a racemic mixture of two enantiomers. The racemic drug has unusual pharmacokinetic properties because of its concentration-dependent binding to plasma proteins in the therapeutic plasma concentration range. This study examined, in healthy subjects, the individual pharmacokinetic properties of both total and unbound d- and 1-disopyramide in plasma after intravenous administration of each enantiomer separately (1.5 mg/kg). Also investigated is the pharmacokinetics of total d- and 1-disopyramide in plasma after intravenous administration of a pseudoracemate. Both d- and 1-disopyramide are found to exhibit concentration-dependent binding to plasma proteins, with d-disopyramide being more avidly bound at lower concentrations. The stereoselective, concentration-dependent binding to plasma proteins resulted in distinct pharmacokinetic properties when the enantiomers were given together as the pseudoracemate. d-Disopyramide had a lower plasma clearance and renal clearance, a longer half-life, and a smaller apparent volume of distribution than 1-disopyramide. However, when the enantiomers were administered separately, there were no differences in the clearance, renal clearance, and volume of distribution between enantiomers calculated from either total or unbound drug concentrations. The results reveal an important pharmacokinetic interaction between the enantiomers of disopyramide when given as a racemic mixture, which may be dose-dependent and is not apparent upon administration of the enantiomers separately.

Adult↗
PubMed1980

Electrophysiologic effects of disopyramide phosphate on reentrant ventricular arrhythmia in conscious dogs after myocardial infarction.

The electrophysiologic actions of disopyramide phosphate on reentrant ventricular tachycardia induced by premature ventricular stimuli were evaluated in conscious dogs 2 to 4 days after myocardial infarction. Disopyramide was administered as a series of intravenous infusions to obtain successive steady state plasma disopyramide concentrations of 1.02 +/- 0.02, 2.05 +/- 0.08, 3.94 +/- 0.09 and 7.69 +/- +/- 0.18 micrograms/ml (mean values +/- standard error of the mean). Disopyramide plasma concentrations of 1.02 +/- 0.02 micrograms/ml produced an increase in the rate and duration of ventricular tachycardia as well as in the interval during which premature ventricular stimuli produced ventricular tachycardia. The effective refractory period of normal myocardium was decreased and conduction (activation time) was improved in ischemic myocardium. Increasing steady state plasma disopyramide concentrations slowed the rate of ventricular tachycardia without decreasing its duration. Slowing of the rate of tachycardia occurred simultaneously with a depression of conduction in normal and ischemic myocardium and an increase in ventricular refractoriness. Induction of ventricular tachycardia was prevented only at steady state plasma disopyramide concentrations of 7.69 +/- 0.18 micrograms/ml. The results of this study suggest that subtherapeutic plasma concentrations of disopyramide may facilitate the development of reentrant ventricular arrhythmia in the electrically unstable heart. Ventricular tachycardia or fibrillation, or both, may be prevented only by plasma disopyramide concentrations that are in excess of the normal therapeutic range of 2 to 4 micrograms/ml.

Animals↗
PubMed1989

Effect of disopyramide on initiation of atrial fibrillation and relation to effective refractory period.

Electrophysiologic studies were performed before and after intravenous administration of disopyramide (2 mg/kg) to 40 patients with either documented or suspected atrial fibrillation (AF). In control studies, sustained AF (greater than 1 minute), nonsustained AF (1 to 60 seconds) and no AF were found in 14, 18 and 8 patients, respectively. After disopyramide, the ability to initiate AF was totally lost in 18 patients (group A), while 22 patients (group B) showed sustained AF (11 patients) or nonsustained AF (11 patients). The effective refractory period of the atrium was 232 +/- 41 ms in the control study and 266 +/- 49 ms after disopyramide. Atrial functional refractory periods before and after disopyramide were 282 +/- 43 and 317 +/- 48 ms, respectively. The differences and ratios of the refractory periods after and before disopyramide were higher in group A than in group B (p less than 0.001). The prolongation of atrial refractoriness after disopyramide was important to suppress the initiation of AF in group A. In some group B patients, on the other hand, the initiation of AF was promoted after disopyramide. Disopyramide may alter the atrial electrophysiologic substrate required for AF initiation.

Atrial Fibrillation↗
PubMed1987

Total and free disopyramide by fluorescence polarization immunoassay and relationship between free fraction and alpha-1 acid glycoprotein.

Disopyramide is an antiarrhythmic drug with concentration dependent protein binding within the therapeutic range. We found good agreement between fluorescence polarization immunoassay (FPIA, Abbott TDX) and high performance liquid chromatography (HPLC) for total disopyramide among 27 admission patients' sera (FPIA = 1.12 (HPLC) -0.002, r = 0.982, SEE = 0.378 mg/l). Agreement between FPIA and HPLC for free disopyramide was similarly good (FPIA = 0.867 (HPLC) -0.003, r = 0.986, SEE = 0.09 mg/l, n = 27). Serum alpha 1 acid glycoprotein concentration (AAG) and free fraction (FF) percent of disopyramide correlated inversely (FF = -0.0112 (AAG) + 31.3 r = 0.707, SEE = 6.41 mg/l, n = 24), and the free disopyramide fraction varied greatly. For two pooled sera with 12 different disopyramide concentrations (range from 0.5-20.0 mg/l), the proportion of free fraction ranged from 6.5 to 73.2%. Overall, we found the free disopyramide fraction variable with each individual, total drug, and protein concentration. Therefore, free drug concentration should be monitored in disopyramide therapy, and FPIA is reliable for free as well as total drug assay.

Chromatography, High Pressure Liquid↗
PubMed1998

Mechanism of compound- and species-specific food effects of structurally related antiarrhythmic drugs, disopyramide and bidisomide.

PURPOSE: To determine mechanism of food effects observed with bidisomide but not with the structurally similar drug, disopyramide. METHODS: Food effect studies of bidisomide and disopyramide were conducted with and without a standardized high fat meal in healthy subjects and in the dog. Intestinal metabolism of disopyramide and absorption of the metabolites were examined after oral administration of the drug to the dogs with portal vein canula implanted. Effects of food or a mixture of amino acids on metabolism of [14C]disopyramide were examined after intraportal infusion of the drug with and without high fat meal and after drug infusion into portal vein with the amino acid mixture, respectively. RESULTS: The systemic availability of bidisomide was markedly reduced with food in humans, whereas the systemic availability of disopyramide did not change notably. In the dog, the systemic availability of bidisomide was also reduced with food. The systemic availability of disopyramide did not change with food. This was due to the fact that reduction in absorption was compensated by reduction of metabolism. There was no evidence for reduction in hepatic and intestinal metabolism with food. CONCLUSIONS: The apparent reduction in disopyramide metabolism with food may be due to an increase in colonal and/or lymphatic absorption. Food effects on the apparent systemic availability of bidisomide and disopyramide in the dog were similar to those in the rat. However, there was substantial species difference in the mechanism of food effects.

Adult↗
PubMed1997

Mechanisms of food effects of structurally related antiarrhythmic drugs, disopyramide and bidisomide in the rat.

PURPOSE: To determine whether the rat is a good animal model for the food effects observed with bidisomide but not with the structurally similar antiarrhythmic drug, disopyramide in man and to explore a reason for the differences in the food effects of these compounds. METHODS: The following effects on the absorption of bidisomide and/or disopyramide were examined in the rat: Food effects, gastrointestinal transit time under fasting and nonfasting conditions, pH effects, hypertonic solution effect of NaCl and glucose, bile effects, permeability, inhibitory effects by Gly, Gly-Gly, Gly-Pro, glucose and mannitol and drug binding to food. RESULTS: Remarkable food effects were observed with bidisomide but not with disopyramide. There was no difference in the GI transit time with and without food. The pH effect with and without food was similar. Effect of salt concentrations on bidisomide and disopyramide was similar. There was no bile effect on absorption of both compounds. Binding of bidisomide and disopyramide to food was similarly low. The apparent permeability of bidisomide was much lower than disopyramide especially in the ileum and its absorption was more inhibited by Gly, Gly-Gly and Gly-Pro. CONCLUSIONS: In the rat, as previously seen in humans, the food effect was observed with bidisomide but not with disopyramide. This difference was in part due to both lower intestinal permeability of bidisomide compared to disopyramide and greater inhibition of absorption by the amino acid, Gly and the dipeptides, Gly-Gly and Gly-Pro.

Animals↗
PubMed1984

Serum disopyramide concentrations and suppression of ventricular premature contractions.

Serum disopyramide determinations and 24-hour Holter monitoring were performed in 20 cardiac subjects with ventricular premature contractions (VPCs) after the first, seventeenth, and thirty-seventh doses of disopyramide, 100 mg (10 subjects; low-dose group) or 200 mg (10 subjects; high-dose group) every 6 hr for 10 days to assess the ability of single- or first-dose data to predict serum disopyramide concentrations at steady state and the relationship between steady-state serum disopyramide concentrations and VPC suppression. Control Holter recordings were made for 48 hr in each subject. There were strong correlations in both groups between data for the AUC over 0 to 6 hr for the first dose (AUC60) and average (C ss) and trough (C min) steady-rate serum disopyramide concentrations after the seventeenth and thirty-seventh doses and the two combined. C ss and C min were related to AUC60 by the following expressions for both dosage groups: C ss = 0.22 AUC60 + 0.90 and C min = 0.20 AUC60 + 0.70. There were good correlations between 6-hr serum disopyramide concentration after the first dose and C ss and C min. There was strong correlation between overall average steady-state serum disopyramide concentration and suppression of VPC frequency. The relationship between VPC suppression and overall average trough serum disopyramide concentration at steady state, on the other hand, was weak.

Administration, Oral↗
PubMed1992

Rapid infusions of bidisomide or disopyramide in conscious dogs: effect of myocardial infarction on acute tolerability.

The acute tolerability of rapid infusions of bidisomide or disopyramide was evaluated in normal conscious dogs and in conscious dogs 48 h after the creation of myocardial infarctions (MIs). Both drugs were given in total doses of 15 mg/kg (1.5 x the canine antiarrhythmic dose for each drug). Bidisomide was well tolerated at infusion rates of 3, 5, 11, and 15 mg/kg/min by normal dogs. Disopyramide was well tolerated, except for anticholinergic effects, by normal dogs given infusions at rates of 1.5 and 3 mg/kg/min. Disopyramide caused a ventricular arrhythmia at 4.5 mg/kg/min in one dog, however. Bidisomide (15 mg/kg/min) was well tolerated and antiarrhythmic in dogs with infarctions. Disopyramide (3 and 4.5 mg/kg/min) was lethal in dogs that had myocardial infarctions. A 1 mg/kg/min infusion rate of disopyramide was antiarrhythmic and well tolerated, except for anticholinergic effects, in the post-MI dogs. Both drugs prolonged the ECG lead II P duration, PR interval (bidisomide more so than disopyramide), and QRS duration. Both bidisomide and disopyramide shifted the mean electrical axis of the QRS complex from a right axis deviation to the normal range in dogs with infarctions. The data indicated that the desired cardiac electropharmacologic effects of bidisomide can be achieved in a 1 min infusion. Normal dogs, and especially dogs with infarctions, revealed the potential hazards of rapidly infusing disopyramide.

Animals↗
PubMed1998

Vasoconstrictor and vasodilator effects of disopyramide on isolated rat vascular smooth muscle.

We investigated the effects of disopyramide on the isometric contractions and intracellular Ca2+ concentrations ([Ca2+]i) measured by Fura-2 fluorescence in isolated rat aorta and portal veins. Disopyramide at concentrations > or = 10(-5) M increased the duration and complexity of the spontaneous contractions in rat portal veins. At > 10(-6) M, it induced a concentration-dependent contraction in the rat aorta. This effect was endothelium independent, associated with an increase in [Ca2+]i and abolished in aortic rings incubated in Ca2+-free solution or pretreated with 10(-7) M nifedipine, suggesting that disopyramide increased [Ca2+]i through the activation of L-type Ca2+ channels. In aortic rings precontracted by KCl (30 and 80 mM), 80 mM KCl in a low-concentration (26.2 mM) Na+ solution or 10(-5) M noradrenaline, disopyramide induced a concentration-dependent relaxation. The relaxant response in 80 mM KCl-precontracted arteries was associated with a parallel reduction in [Ca2+]i, an effect attributable to its Ca2+ channel blocking properties. In contrast, disopyramide had no effect on the concentration-response curves to noradrenaline in the presence of nifedipine. Disopyramide also inhibited in a concentration-dependent manner the relaxation induced by levcromakalim in aortic rings precontracted by 30 mM KCl because of its inhibitory action on K(ATP) channels, whereas it had no effect on the relaxant response to sodium nitroprusside. These effects, together with the negative inotropic effects of the drug, may account for the increase in mean arterial pressure observed in disopyramide-treated patients and the profound hypotension observed after overdosages of disopyramide.

Animals↗
PubMed1981

The effect of enzyme induction on the metabolism of disopyramide in man.

1 The effects of rifampicin, phenytoin, and disopyramide treatments on the metabolism of disopyramide were studied in patients and volunteers. 2 Rifampicin treatment markedly increased the metabolism of disopyramide. 3 Phenytoin had effects similar to those of rifampicin. The effect subsided in 2 weeks after stopping the treatment. 4 The metabolism of disopyramide seemed fastest in the patient group with the higher dose of disopyramide. Both in patients and volunteers a significant increase occurred in the urinary mono-N-dealkyldisopyramide/disopyramide ratio during the first week of disopyramide therapy. This change can partly be due to pharmacokinetic differences between disopyramide and its metabolite. The inducing effect of disopyramide remained uncertain.

Adult↗
PubMed1994

Low dose disopyramide often fails to prevent neurogenic syncope during head-up tilt testing.

Low dose disopyramide has been used to prevent neurally-mediated syncope during head-up tilt testing but a correlation between blood levels and efficacy has not been described. We measured disopyramide levels in 15 patients with recurrent syncope and positive 70 degrees head-up tilt tests who underwent one or more repeat tests on the drug. There were 9 males and 6 females, age range 15-78 years. Fourteen of the 15 patients had structurally normal hearts. The daily disopyramide dose was 645 +/- 165 mg (mean +/- SD). Patients developed syncope during 9 tests and had no syncope during 12 tests. The mean disopyramide level in patients with positive tests was significantly lower than the level in patients with negative tests (2.4 +/- 0.15 mu/mL vs 3.2 +/- 0.22 mu/mL, P = 0.018). Six patients were tested twice on different disopyramide doses. Five of these six patients had syncope during head-up tilt testing on the lower dose and negative tests on the higher dose (disopyramide levels 2.2 +/- 0.17 mu/mL vs 3.2 +/- 0.17 mu/mL, P = 0.004). Thus, disopyramide is effective in preventing neurogenic syncope during head-up tilt testing, but higher blood levels are often necessary for efficacy. In a given patient, failure to respond to low dose disopyramide does not preclude success on higher doses.

Adolescent↗
PubMed1989

Study on transport of disopyramide into the intestinal lumen aimed at gastrointestinal dialysis by activated charcoal in rats.

The characteristics of exsorption and/or excretion of disopyramide into the gastrointestinal lumen have been investigated after intravenous administration of the drug at doses of 10 and 30 mg kg-1 to rats by the in-situ single pass perfusion technique. Disopyramide was appreciably excreted into the bile where its levels were approximately ten-fold higher than those in the serum. The exsorption rate of disopyramide and mono-N-dealkyldisopyramide (MND) into the perfusate was increased with an increase in the serum level following an increase from 10 to 30 mg kg-1 in the dose of disopyramide. The average amounts of disopyramide exsorbed into the perfusate were 17.0 and 18.4% at the dose of 10 and 30 mg kg-1, respectively, whereas those of MND were less than 1% at both doses of disopyramide. Oral administration of activated charcoal reduced the serum disopyramide levels after intravenous administration of the drug (20 mg kg-1) compared with the control treatment. By oral administration of activated charcoal, t 1/2 and AUC were decreased to 89 and 82%, respectively, and Cltot was increased to 122% compared with the corresponding control treatment. Vd was not different between the treated rats and control rats. These results suggest that the oral administration of activated charcoal can enhance the clearance of disopyramide and MND from the blood.

Administration, Oral↗