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Annals of the New York Academy of... Jul 1971
Topics: Administration, Oral; Arrhythmias, Cardiac; Blood Urea Nitrogen; Half-Life; Humans; Injections, Intramuscular; Injections, Intravenous; Intestinal Absorption; Kinetics; Procainamide
PubMed: 5285382
DOI: 10.1111/j.1749-6632.1971.tb46914.x -
Clinical Pharmacology and Therapeutics Mar 1975To investigate the effect of end stage renal insufficiency and hemodialysis on the serum half-life of procainamide, 500 mg of procainamide was given orally to control...
To investigate the effect of end stage renal insufficiency and hemodialysis on the serum half-life of procainamide, 500 mg of procainamide was given orally to control subjects and dialysis patients on interdialysis days. Procainamide was assayed by spectrophotometry and spectrophotofluorometry. Mean half-life in normal subjects was 3.2 hr by spectrophotometry and 3.5 hr by spectrophotofluorometry. Mean half-life in patients was 11.3 hr by spectrophotometry and 16.0 hr by spectrophotofluorometry (p less than 0.001 compared to control subjects). Half-life of procainamide during dialysis in patients given 500 mg of procainamide 1 hr before dialysis was 4.3 hr and 9.6 hr on a nondialysis day (p less than 0.001). Both methods of assay gave higher levels of procainamide when the metabolite, N-acetylprocainamide, was present in serum and the extract allowed to stand in 1 N HCl, but spectrophotometry was less affected. Thus, end stage renal insufficiency greatly prolongs the half-life of procainamide, procainamide is readily dialyzable, and N-acetylprocainamide is hydrolyzed in 1 N HCl to procainamide during routine serum determinations.
Topics: Acetylation; Female; Half-Life; Humans; Kidney Failure, Chronic; Male; Procainamide; Renal Dialysis; Spectrometry, Fluorescence
PubMed: 1120398
DOI: 10.1002/cpt1975173321 -
Journal of Cardiovascular... Apr 1994Although intravenously administered procainamide has been used extensively during electropharmacologic testing for more than 10 years, there is little information...
INTRODUCTION
Although intravenously administered procainamide has been used extensively during electropharmacologic testing for more than 10 years, there is little information available on the effects of incremental dosing of procainamide in patients with inducible, monomorphic ventricular tachycardia (VT).
METHODS AND RESULTS
Twenty-nine patients with coronary artery disease had sustained monomorphic VT reproducibly induced in the baseline, drug-free state. Programmed stimulation was repeated 5 minutes after loading infusion (50 mg/min) of 7.5 and 15 mg/kg (all patients) and 22.5 mg/kg of procainamide (15 patients), while maintaining continuous infusion of 0.055, 0.11, and 0.165 mg/kg per minute after each increment in dose, respectively. Corresponding procainamide plasma concentrations were 5.6 +/- 2, 10.5 +/- 3, and 14.5 +/- 3 mg/L before, and 4.7 +/- 2, 9.6 +/- 3, and 14.6 +/- 4 mg/L after electrophysiologic study at each increment in dose of procainamide, respectively. Each incremental dose of procainamide resulted in significant prolongation of tachycardia cycle length and QRS duration during sinus rhythm and right ventricular pacing. Five (17%), 7 (24%), and 1 (7%) patients, respectively, had no inducible sustained VT following the incremental dosing of procainamide. Three of five patients who had no inducible VT at 7.5 mg/kg had VT induced again at a higher dose of procainamide. Four of 24 patients whose VT remained inducible at 7.5 mg/kg of procainamide had no VT induced at 15 mg/kg of procainamide. Twelve (41%), 15 (52%), and 6 (40%) patients, respectively, no longer had VT with baseline morphology induced following the incremental dosing of procainamide. VT with new morphology compared to baseline was induced in more than 40% of patients at one or more of the three different procainamide dosing regimens. The mean cycle length of VTs with new morphology was significantly shorter than the cycle length of tachycardias with baseline morphology at each particular dose of procainamide.
CONCLUSION
Similar serum procainamide concentrations before and after programmed stimulation can be achieved at the described dosing regimen. Although 7.5 and 15 mg/kg of procainamide are both effective in suppressing induction of all VT in 20% to 25% of patients, non-inducibility at a particular dose of procainamide does not predict noninducibility at a respectively higher or lower dose. New morphologies of VT that are frequently faster than VTs with baseline morphology at a particular dose of procainamide can be induced in approximately half of the patients, and the clinical significance of these arrhythmias remains to be determined.
Topics: Adult; Aged; Aged, 80 and over; Cardiac Pacing, Artificial; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Osmolar Concentration; Procainamide; Refractory Period, Electrophysiological; Tachycardia, Ventricular
PubMed: 8019707
DOI: 10.1111/j.1540-8167.1994.tb01168.x -
The American Journal of Cardiology Jan 1988No previous studies have determined the pharmaco-dynamics of intravenous procainamide when administered in a dose of 15 mg/kg and at a rate of 50 mg/min, as is common...
No previous studies have determined the pharmaco-dynamics of intravenous procainamide when administered in a dose of 15 mg/kg and at a rate of 50 mg/min, as is common practice during electropharmacologic testing. In this study, 30 patients received procainamide in this fashion; the right ventricular effective refractory period and the QRS duration at a ventricular pacing rate of 120/minute were then determined every minute for 20 minutes. Ten patients received no maintenance infusion of procainamide (group A), 10 received a 4 mg/min maintenance infusion (group B) and 10 received an 8 mg/min maintenance infusion (group C). Ten additional patients received no procainamide and served as control subjects (group D). The plasma procainamide concentration was measured at 1, 5, 10, 15 and 20 minutes after the loading dose was administered. A stable plasma procainamide concentration was not present in group A, B, or C until 15 minutes after infusion of the loading dose. The effective refractory period and QRS duration increased compared with baseline at 1 minute, decreased between 1 and 10 minutes and then remained essentially unchanged between 10 and 20 minutes in all 3 treatment groups. Concentration-effect relation was linear in each treatment group. The plasma procainamide concentrations in group C were significantly greater than in group A; however, the effects on refractoriness and QRS duration were similar in both groups. These findings indicate that with a procainamide dosing method commonly used during electropharmacologic testing, the plasma procainamide concentration decreases significantly during the first 15 minutes after the loading dose is administered.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Aged; Arrhythmias, Cardiac; Electrocardiography; Female; Heart Conduction System; Humans; Infusions, Intravenous; Male; Middle Aged; Procainamide; Refractory Period, Electrophysiological
PubMed: 3337024
DOI: 10.1016/0002-9149(88)91311-2 -
Journal of Chromatography. B,... Jan 2023N-glycans in glycoproteins can affect physicochemical properties of proteins; however, some reported N-glycan structures are inconsistent depending on the type of...
Peptide-N-glycosidase F or A treatment and procainamide-labeling for identification and quantification of N-glycans in two types of mammalian glycoproteins using UPLC and LC-MS/MS.
BACKGROUND
N-glycans in glycoproteins can affect physicochemical properties of proteins; however, some reported N-glycan structures are inconsistent depending on the type of glycoprotein or the preparation methods.
OBJECTIVE
To obtain consistent results for qualitative and quantitative analyses of N-glycans, N-glycans obtained by different preparation methods were compared for two types of mammalian glycoproteins.
METHODS
N-glycans are released by peptide-N-glycosidase F (PF) or A (PA) from two model mammalian glycoproteins, bovine fetuin (with three glycosylation sites) and human IgG (with a single glycosylation site), and labeled with a fluorescent tag [2-aminobenzamide (AB) or procainamide (ProA)]. The structure and quantity of each N-glycan were determined using UPLC and LC-MS/MS.
RESULTS
The 21 N-glycans in fetuin and another 21 N-glycans in IgG by either PF-ProA or PA-ProA were identified using LC-MS/MS. The N-glycans in fetuin (8-13 N-glycans were previously reported) and in IgG (19 N-glycans were previously reported), which could not be identified by using the widely used PF-AB, were all identified by using PF-ProA or PA-ProA. The quantities (%) of the N-glycans (>0.1 %) relative to the total amount of N-glycans (100 %) obtained by AB- and ProA-labeling using LC-MS/MS had a similar tendency. However, the absolute quantities (pmol) of the N-glycans estimated using UPLC and LC-MS/MS were more efficiently determined with ProA-labeling than with AB-labeling. Thus, PF-ProA or PA-ProA allows for more effective identification and quantification of N-glycans than PF-AB in glycoprotein, particularly bovine fetuin. This study is the first comparative analysis for the identification and relative and absolute quantification of N-glycans in glycoproteins with PF-ProA and PA-ProA using UPLC and LC-MS/MS.
Topics: Animals; Cattle; Humans; Chromatography, Liquid; Glycoproteins; Immunoglobulin G; Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; Peptides; Polysaccharides; Procainamide; Tandem Mass Spectrometry
PubMed: 36493594
DOI: 10.1016/j.jchromb.2022.123538 -
Therapeutic Drug Monitoring 1986Procainamide is used in antiarrhythmic therapy, and the need to monitor the drug concentration as well as its major plasma metabolite, N-acetyl-procainamide, is well... (Comparative Study)
Comparative Study
Procainamide is used in antiarrhythmic therapy, and the need to monitor the drug concentration as well as its major plasma metabolite, N-acetyl-procainamide, is well established. An assay designed for the routine clinical therapeutic drug monitoring laboratory has been developed. A 0.5-ml aliquot of blood plasma is treated with 0.1 ml of internal standard solution, and the mixture is alkalinized. The drug, its metabolite, and the internal standard, N-propionyl procainamide are extracted with methylene chloride. After evaporation to dryness and addition of 0.3 ml of mobile phase, a volume of 0.1 ml is injected onto a liquid chromatograph equipped with spectrofluorimetric detection, which has a better specificity than UV absorptiometric detection. The between-day coefficient of variation was 3.5% for procainamide and 5% for N-acetylprocainamide. The sensitivity of this technique permits detection of 0.1 micrograms/ml of procainamide and 0.25 micrograms/ml of N-acetylprocainamide. Several drugs that are often present in patients receiving procainamide were shown not to interfere.
Topics: Acecainide; Chromatography, High Pressure Liquid; Humans; Procainamide; Spectrometry, Fluorescence
PubMed: 2428144
DOI: 10.1097/00007691-198609000-00023 -
The American Journal of Cardiology Aug 1983Ventricular arrhythmias after Q-T prolongation by drugs could result from a nonhomogeneous increase in refractoriness (dispersion). Dispersion of effective refractory...
Ventricular arrhythmias after Q-T prolongation by drugs could result from a nonhomogeneous increase in refractoriness (dispersion). Dispersion of effective refractory periods (ERP) was measured before and after infusion of 1 g of procainamide using twice-threshold extrastimuli applied in sinus rhythm and with 500 ms ventricular drive cycle length at 3 right ventricular sites (2 patients) or 2 right and 1 left ventricular site (10 patients). Procainamide prolonged ERP. In drive, average ERP was 247 +/- 5 ms (standard error of the mean) before and 277 +/- 7 ms after procainamide (p less than 0.001). The Q-T interval was prolonged by 50 ms in drive (p less than 0.001), but Q-T prolongation did not reflect the increased ERP (r =-0.05). However, procainamide did not alter measured dispersion (54 +/- 16 to 44 +/- 14 ms in sinus, 48 +/- 14 to 47 +/- 13 ms in drive). Polymorphic ventricular tachycardia (VT) was induced in 6 patients in whom drive itself generally failed to reduce dispersion, and failure to induce tachycardia or shorter runs after procainamide was associated with narrowed dispersion. Polymorphic VT was not induced after procainamide in 2 patients with clinical episodes of torsades de pointes caused by type I agents. The mechanism of torsades de pointes was not explained by dispersion of refractoriness or by polymorphic VT initiated by premature beats after a type I drug.
Topics: Aged; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Procainamide
PubMed: 6869273
DOI: 10.1016/0002-9149(83)90122-4 -
Journal of Clinical Pharmacology Jan 1996Dosage reduction of procainamide has been recommended in patients with congestive heart failure (CHF). However, these recommendations are based primarily on studies with... (Clinical Trial)
Clinical Trial
Dosage reduction of procainamide has been recommended in patients with congestive heart failure (CHF). However, these recommendations are based primarily on studies with unmatched control groups, suboptimal blood sampling, and in patients not receiving angiotensin-converting enzyme (ACE) inhibitors. These agents increase renal blood flow, which theoretically may offset alterations in drug disposition in patients with CHF. The pharmacokinetics of procainamide in patients with chronic CHF and in matched controls were compared. A single intravenous dose of 750 mg of procainamide was administered to 9 patients with chronic New York Heart Association (NYHA) class II or III CHF (mean +/- SD left ventricular ejection fraction 22 +/- 9%) receiving medical therapy and 7 control subjects matched for age and gender. Blood and urine samples were collected at intervals over a period of 48 and 72 hours, respectively. Patients with CHF and control subjects were demographically similar, with the exception of concomitant medications, including ACE inhibitors (8/9 versus 1/7, respectively). There were no significant differences between patients with CHF and control subjects in mean +/- SD peak serum concentrations (Cmax), area under the serum concentration-time curve (AUC0-infinity), total clearance, renal clearance, half-life (t1/2), or volume of distribution (Vd) of procainamide. Similarly, there were no significant differences between patients with CHF and control subjects in the mean +/- SD Cmax, AUC0-infinity, renal clearance, or t1/2 of N-acetylprocainamide (NAPA). Procainamide dosage reduction may not be necessary in patients with chronic stable CHF who are receiving medical therapy.
Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Procainamide
PubMed: 8932541
DOI: 10.1002/j.1552-4604.1996.tb04149.x -
Clinical Pharmacology and Therapeutics Oct 1977The pharmacokinetics of procainamide (PA) and N-acetylprocainamide (NAPA) were compared in 3 normal subjects after simultaneous intraveous injection of PA and NAPA-13C....
The pharmacokinetics of procainamide (PA) and N-acetylprocainamide (NAPA) were compared in 3 normal subjects after simultaneous intraveous injection of PA and NAPA-13C. The distribution kinetics of both compounds were modeled with a 3-compartment mamillary system, and it was found that their steady-state distribution volumes were not significantly different, averaging 1.41 L/kg for PA and 1.46 L/kg for NAPA. However, the intercompartmental clearances of NAPA were slower than those of PA. In these normal subjects, the average elimination t1/2 and total elimination clearance for PA were 2.5 hr and 589.8 ml/min, and for NAPA were 6.2 hr and 233.7 ml/min. Mean renal clearances of PA (346.7 ml/min) and of NAPA (199.5 ml/min) exceeded the usual rate of glomerular filtration, which suggests that both compounds are eliminated in part by renal tubular secretion. All subjects were phenotypic rapid acetylators of isoniazid and converted approximately one fourth of the administered PA dose to NAPA-12C. The fate of 15.4% of the administered PA and 14.5% of the administered NAPA-13C was not determined.
Topics: Acetylation; Adult; Carbon; Carbon Isotopes; Computers; Humans; Kinetics; Male; Models, Biological; Procainamide; Statistics as Topic
PubMed: 902457
DOI: 10.1002/cpt1977224447 -
The Canadian Journal of Cardiology 1986A 59-year old female with history of benign ventricular ectopy who developed sustained monomorphic ventricular tachycardia (VT) during therapy with procainamide is...
A 59-year old female with history of benign ventricular ectopy who developed sustained monomorphic ventricular tachycardia (VT) during therapy with procainamide is reported. The tachycardia occurred 24 hours after institution of procainamide without any other evidence of drug toxicity or QT prolongation. When procainamide was withheld, VT resolved completely and no arrhythmia could be induced by programmed ventricular stimulation. When the patient was rechallenged with procainamide at therapeutic level, sustained monomorphic VT was initiated reproducibly by programmed ventricular stimulation. Without antiarrhythmic therapy, patient has been asymptomatic and free of recurrent VT after a follow-up of 9 months. This case: Demonstrates that procainamide may cause the first emergence of sustained monomorphic VT in a patient with no previous history of VT; and Emphasizes the utility of programmed ventricular stimulation in providing direct evidence for drug mediated exacerbation of the ventricular arrhythmia.
Topics: Bundle-Branch Block; Cardiac Complexes, Premature; Cardiac Pacing, Artificial; Electrocardiography; Female; Heart Ventricles; Humans; Middle Aged; Procainamide; Tachycardia
PubMed: 2420424
DOI: No ID Found