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Clinical Pharmacology and Therapeutics Jun 1987The effects of amiodarone on the pharmacokinetic and electrophysiologic properties of procainamide were examined in eight patients treated for recurrent ventricular...
The effects of amiodarone on the pharmacokinetic and electrophysiologic properties of procainamide were examined in eight patients treated for recurrent ventricular arrhythmias who received intravenous procainamide, 6 to 15 mg/kg, at control and after 1 to 2 weeks of oral amiodarone treatment. Compared with control, procainamide plasma clearance decreased from 0.43 +/- 0.12 L/kg-hr to 0.33 +/- 0.12 L/kg-hr (P less than 0.01), plasma elimination half-life increased from 3.77 +/- 0.64 hours to 5.21 +/- 0.42 hours (P less than 0.01), and volume of distribution was unchanged from 2.31 +/- 0.74 L/kg to 2.47 +/- 0.90 L/kg during amiodarone treatment. As single agents, intravenous procainamide and oral amiodarone produced equivalent increases in QRS duration, rate-corrected QT interval, right ventricular effective refractory period, and cycle length of induced ventricular tachycardia. After the addition of intravenous procainamide to amiodarone the QRS duration, rate-corrected QT interval, and, in six of eight patients, ventricular tachycardia cycle length were significantly increased compared with control or either drug alone, suggesting additive electrophysiologic effect. However, acceleration of induced ventricular tachycardia occurred in one patient with combined treatment, suggesting a potential for adverse electrophysiologic interactions. These findings indicate that amiodarone has pharmacokinetic and electrophysiologic interactions with procainamide and suggest that the intravenous dose of procainamide be reduced by 20% to 30% during concurrent drug administration.
Topics: Aged; Amiodarone; Drug Interactions; Electrocardiography; Female; Heart; Heart Ventricles; Humans; Infusions, Intravenous; Kinetics; Male; Middle Aged; Procainamide; Tachycardia; Ventricular Fibrillation
PubMed: 3581646
DOI: 10.1038/clpt.1987.82 -
The American Journal of Cardiology May 1974
Topics: Adult; Aged; Electrocardiography; Heart Atria; Heart Conduction System; Humans; Middle Aged; Procainamide; Refractory Period, Electrophysiological; Spectrophotometry; Time Factors
PubMed: 4820891
DOI: 10.1016/0002-9149(74)90248-3 -
Clinical Pharmacology and Therapeutics Sep 1976The kinetics of a measure of pharmcologic effect (prolongation of the QT interval) of procainamide, as well as the kinetics of the plasma concentration, urine excretion,...
The kinetics of a measure of pharmcologic effect (prolongation of the QT interval) of procainamide, as well as the kinetics of the plasma concentration, urine excretion, and saliva concentration of the drug were investigated in 14 trials in 4 subjects. A single 500-mg dose was given by rapid intravenous infusion, and frequent subsequent determinations of the above variables were made. A 2-compartment pharmacokinetic model with a third compartment for the saliva was used to fit the plasma, urine, and saliva data simultaneously. Analysis of the data reveals that the kinetics of the drug concentrations in saliva and of the pharmacologic effect are indistinguishable. They both must be considered to be different from those of the drug concentrations in plasma. Thus, in normal individuals under the conditions of this study, saliva concentrations more precisely indicate the time-course of drug at a cardiac site of action, although they do not parallel plasma drug concentrations until 6 hr or more after a rapid intravenous infusion. The following average pharmacokinetic parameters for plasma were found: terminal half-life, 2.9 hr; total clearance, 828 ml/min; renal clearance, 334 ml/min; and steady-state volume of distribution, 180 L. Average distribution pseudoequilbrium half-time (t1/2 alpha) was 5.2 min from an initial volume of distribution of 36.6 L.
Topics: Electrocardiography; Heart Rate; Humans; Kinetics; Male; Models, Biological; Procainamide; Saliva
PubMed: 954350
DOI: 10.1002/cpt1976203278 -
American Journal of Hospital Pharmacy Nov 1991The extent to which the procainamide-dextrose complex reverts to free procainamide hydrochloride in plasma was studied in vitro. The procainamide-dextrose species was...
The extent to which the procainamide-dextrose complex reverts to free procainamide hydrochloride in plasma was studied in vitro. The procainamide-dextrose species was formed, isolated using preparative liquid chromatography, and then added to six different lots of pooled plasma that were maintained at physiological temperature (37 +/- 0.1 degrees C). At zero, four, and eight hours after preparation of the samples, 1-mL portions were removed from each sample, extracted, and assayed for procainamide hydrochloride using high-performance liquid chromatography. The mean procainamide hydrochloride concentrations at zero, four, and eight hours after preparation were 2.67, 4.81, and 1.38 g/mL, respectively. Each lot of pooled plasma was statistically analyzed to determine if a significant amount of procainamide hydrochloride reappeared. Analysis of variance showed significant difference between the concentrations of free procainamide hydrochloride in the samples at zero, four, and eight hours (p less than 0.02). Follow-up with Duncan's multiple comparisons test determined that the mean procainamide hydrochloride concentrations immediately after preparation were not significantly different from those at eight hours, but the mean procainamide hydrochloride concentrations at four hours were significantly different from those at eight hours (p less than 0.01). A paired Student's t test comparing the data from zero and eight hours showed a significant reduction in mean procainamide hydrochloride concentrations with time (p less than 0.05). The procainamide-dextrose complex in vitro does not revert to free procainamide hydrochloride in plasma at physiological temperature during the first eight hours.
Topics: Drug Compounding; Drug Stability; Glucose; Humans; Procainamide; Solutions
PubMed: 1746577
DOI: No ID Found -
The American Journal of Cardiology Sep 1986Eighteen patients were given quinidine and procainamide separately to evaluate whether prolongation of the QT interval by type Ia antiarrhythmic agents is a... (Comparative Study)
Comparative Study
Eighteen patients were given quinidine and procainamide separately to evaluate whether prolongation of the QT interval by type Ia antiarrhythmic agents is a drug-specific phenomenon. Doses were titrated to achieve standard trough therapeutic levels of quinidine (2 to 5 micrograms/ml) and procainamide (4 to 12 micrograms/ml). In 16 of the 18 patients, the increase in corrected QT interval (QTc) was greater with quinidine than with procainamide, averaging 78 +/- 10 ms (+/- standard error of the mean) with quinidine and 39 +/- 7 ms with procainamide (p less than 0.001). The greater degree of QTc prolongation with quinidine than with procainamide was not due to differences in sinus cycle length, QRS duration, serum potassium level or concomitant drug therapy. Differences in relative drug level did not appear to account for the greater effect of quinidine. Thus, at frequently used plasma levels, quinidine prolongs QTc to a greater degree than does procainamide. This effect does not appear to be due to the comparison of "nonequivalent" drug levels.
Topics: Adult; Aged; Arrhythmias, Cardiac; Electrocardiography; Female; Humans; Male; Middle Aged; Procainamide; Quinidine
PubMed: 3751914
DOI: 10.1016/0002-9149(86)90025-1 -
Journal of Pharmaceutical Sciences Dec 1975A GLC method for the determination of procainamide in biological fluids is presented. By using a dipropyl analog of procainamide as an internal standard, both compounds...
A GLC method for the determination of procainamide in biological fluids is presented. By using a dipropyl analog of procainamide as an internal standard, both compounds can be chromatographed directly, yielding linear calibration curves and a sensitivity that allows quantitative determination of concentrations as low as 0.1 mug/ml. The extraction procedure was carefully modified to avoid hydrolysis of N-acetylprocainamide, a major metabolite of procainamide. The usefulness of the procedure is demonstrated by following the disappearance of procainamide from the plasma and urine of human subjects treated with the drug.
Topics: Chromatography, Gas; Humans; Hydrolysis; Methods; Procainamide
PubMed: 1206490
DOI: 10.1002/jps.2600641213 -
European Journal of Clinical... Jul 1974
Topics: Absorption; Adult; Ammonium Chloride; Bicarbonates; Cheek; Humans; Hydrogen-Ion Concentration; Kidney; Procainamide; Spectrophotometry
PubMed: 4850327
DOI: 10.1007/BF00560346 -
Circulation Dec 1987We studied the effects of procainamide and N-acetylprocainamide (NAPA) in a conscious dog preparation of atrial flutter resulting from circus movement around the... (Comparative Study)
Comparative Study
We studied the effects of procainamide and N-acetylprocainamide (NAPA) in a conscious dog preparation of atrial flutter resulting from circus movement around the tricuspid orifice. We also recorded transmembrane potentials of atrial tissues from the circus path in vitro. In 12 instrumented dogs, average flutter cycle length was 157 msec, the duration of the excitable gap was 73 msec, and conduction velocity was 0.75 m/sec. At 4 and 8 mg/kg, procainamide moderately prolonged cycle length, but did not terminate the flutter. At a cycle length of 300 msec procainamide increased effective refractory period (ERP) by 12% and 20% and conduction time by 8% and 19%. At 16 and 32 mg/kg procainamide prolonged cycle length, ERP, and conduction time by 60% to 80% and stopped the flutter in all trials. NAPA, at 16, 32, and 64 mg/kg, increased flutter cycle length by 16%, 16%, and 31%, ERP by 14%, 28%, and 41%, and conduction time by less than 15%. NAPA terminated the flutter in two of six dogs given 32 mg/kg, and three of five dogs given 64 mg/kg. The excitable gap was lengthened by both procainamide and NAPA. Transmembrane potentials showed that at a cycle length from 1000 to 300 msec procainamide (10 mg/liter) increased action potential duration and decreased the first time derivative of phase O of the action potential (Vmax), whereas NAPA (20 mg/liter) increased action potential duration without changing Vmax. These findings show the difficulty of relating drug effects on transmembrane potentials to efficacy in vivo since the former do not necessarily indicate which changes in cellular electrical activity are responsible for efficacy against a particular arrhythmogenic mechanism.
Topics: Acecainide; Action Potentials; Animals; Atrial Flutter; Dogs; Electrocardiography; Humans; In Vitro Techniques; Membrane Potentials; Procainamide
PubMed: 2445503
DOI: 10.1161/01.cir.76.6.1397 -
Cardiovascular Drugs and Therapy Apr 1997Procainamide is a class IA antiarrhythmic drug indicated for the treatment of life-threatening or symptomatic ventricular arrhythmias. The current sustained-release... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Procainamide is a class IA antiarrhythmic drug indicated for the treatment of life-threatening or symptomatic ventricular arrhythmias. The current sustained-release formulation requires 6-hour dosing (qid). To improve patient compliance, a new sustained-release formulation for twice-daily (bid) administration has been developed (Procanbid, Parke-Davis). This study assesses the pharmacologic equivalence of the bid and qid formulations in the suppression of symptomatic ventricular premature depolarizations (VPDs). Fourteen centers enrolled a total of 99 patients with frequent symptomatic VPDs (average > or = 20 VPDs/hr) who previously responded to and tolerated the procainamide qid formulation. During the first week of the double-blind phase, patients were randomized to either placebo or procainamide dosages of 1000, 2000, or 4000 mg/d (bid or qid formulations). In the second week, the patients were crossed over to the alternate formulation. Seventy-seven patients qualified for the primary activity analysis. The bid and qid formulations showed comparable effectiveness in the suppression of mean VPDs with a linear dose-response relationship. The VPD suppression was not attenuated towards the end of the dosing interval for either formulation. Sixty-eight of these patients entered an optional 1-year extension to receive the bid formulation. Thirty-seven (54%) patients had adverse effects. Of those, 15 (22%) had side effects considered treatment related. Most of the adverse events occurred during the first 6 weeks of treatment. Only a few patients (8%) withdrew as a consequence of treatment with the bid formulation. The overall safety profile of the bid formulation was similar to other formulations, and the procainamide bid formulation has a low proarrhythmic rate (< 3%). In conclusion, the effectiveness of the twice-daily formulation of procainamide in the suppression of VPDs is comparable to the currently available qid formulation.
Topics: Aged; Anti-Arrhythmia Agents; Cross-Over Studies; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Procainamide; Ventricular Premature Complexes
PubMed: 9140693
DOI: 10.1023/a:1007736931662 -
Clinical Pharmacology and Therapeutics Dec 1980Thirty-two patients had blood and urine collected simultaneously for measurement of procainamide, acetylprocainamide, and creatinine. The ratios of drug clearance to...
Thirty-two patients had blood and urine collected simultaneously for measurement of procainamide, acetylprocainamide, and creatinine. The ratios of drug clearance to creatinine clearance were calculated for each. The procainamide:creatinine clearance ratio averaged 2.9 +/- 1.6 (SD) and fell as age of the patients rose (r = 0.5, p < 0.01). The acetylprocainamide:creatinine clearance ratio averaged 1.7 +/- 0.8 and also fell with age. The combination of decline in overall renal function with age with this decrease in the rate of renal tubular secretion of these drugs led to a progressive age-related rise in the steady-state serum level of procainamide (r = 0.56, p < 0.01) and acetylprocainamide (r = 0.36, p < 0.1) achieved by any dose of procainamide. Thus, the dosage of procainamide must be individualized for both overall renal function (GFR) and the age-related variations in renal tubular secretion that are of most note in children and the elderly.
Topics: Acecainide; Adult; Aged; Aging; Child; Creatinine; Humans; Metabolic Clearance Rate; Middle Aged; Procainamide
PubMed: 6160015
DOI: 10.1038/clpt.1980.228