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Biomedical subjects

J M Nappi

Publications and source records attributed to J M Nappi.

28 records · Page 2Linked to original sources
PubMed1984

Pirmenol for control of ventricular arrhythmias: oral dose-ranging and short-term maintenance study.

The antiarrhythmic efficacy and safety of oral pirmenol hydrochloride were assessed during a controlled, dose-ranging and short-term maintenance study in 12 patients with frequent (greater than 480/8 hours) premature ventricular complexes (PVCs). Eleven patients (92%) responded favorably (greater than 70% PVC suppression) to a trial of different doses. Mean interval (8-hour) suppression of PVC frequency was 95% in these 11 and 86% in the entire group. Twenty-four-hour suppression was similar in responders (88%). Repetitive PVCs were essentially eliminated. The mean effective dose was 316 mg/day (105 mg/8 hours). The average predose (trough) plasma concentration at the end of dose ranging was 1.4 micrograms/ml and the drug elimination half-life 7.3 hours (n = 12). Of 11 responding patients, 10 completed a 2-week outpatient trial. Pirmenol continued to be effective and tolerated in 8 patients, maintaining an overall average outpatient PVC suppression of 80%. The electrocardiographic intervals were mildly prolonged after multiple dosing (PR + 7%, QRS + 12%, QTc + 8%; all p less than 0.01). Blood pressure and heart rate did not change during treatment. The echocardiographic ejection fraction was maintained. Thus, oral pirmenol appears to be effective, conveniently administered and well tolerated as an antiarrhythmic agent for control of ventricular extrasystoles.

Administration, Oral↗
PubMed1981

Review of a new gastrointestinal drug--metoclopramide.

The pharmacology, pharmacokinetics, therapeutic and diagnostic uses, toxicity, adverse reactions, and contraindications of metoclopramide are reviewed. Metoclopramide enhances the rate of gastric emptying by (1) augmenting esophageal peristalsis, gastric antral contractions, and small intestine transit time and (2) increasing resting pressures of the lower esophageal and pyloric sphincters. The drug does not stimulate gastric acid secretions. The injectable form is approved for use to facilitate intubation of the small intestine and the passage of barium into the intestine for radiographic procedures. Tablets are approved for the treatment of symptoms associated with diabetic gastroparesis. The drug has been used in the treatment of vomiting of various etiologies. The side effects of metoclopramide are usually mild, transient, and reversible with discontinuation of the drug. They include drowsiness, GI disturbances, extrapyramidal reactions, and increased lactation. Metoclopramide should not be given in combination with MAO inhibitors, tricyclic antidepressants, sympathomimetic amines, or to patients with pheochromocytoma, GI hemorrhage, obstruction, or perforation. Metoclopramide appears to be an effective drug in stimulating the mobility of the upper gastrointestinal tract without increasing gastric secretions. Further studies are needed to assess its value in the treatment of vomiting secondary to anesthesia and chemotherapy, and to assess its precise role in the treatment of diabetic gastroparesis.

Diabetes Complications↗
PubMed1977

Individualization of phenytoin dosage regimens.

Two methods for arriving at optimum, individual phenytoin dosage regimens have been evaluated in 12 patients. (1) Individual Michaelis-Menten pharmacokinetic parameters for phenytoin were estimated from two reliable steady-state phenytoin serum concentrations resulting from different daily doses: The observed steady-state phenytoin serum levels obtained after 3 to 8 wk of compliance with dosage regimens calculated from the individual pharmacokinetic parameters agreed well with predicted levels (r = 0.824, p less than 0.02). The average deviation between observed and predicted levels was 0.04 mug/ml (range, +/- 3.2 mug/ml). (2) A previously published nomogram for making adjustments in phenytoin dosage regimens: The serum phenytoin concentration actually expected from the dose indicated by the nomogram was calculated using individual pharmacokinetic parameters. The daily dose for one patient would have exceeded his estimated maximal rate of metabolism. The correlation between calculated and predicted phenytoin serum levels in the other 11 patients was weak but significant (r= 0.360, p less than 0.05). The average deviation was --3 mug/ml (range, 3.9 to --11.3 mug/ml). It was concluded that the use of individual pharmacokinetic parameters is practical and is also superior to the nomogram.

Adolescent↗
PubMedDate not supplied

Disposition of intravenous pirmenol.

Twelve patients having frequent premature ventricular complexes (PVCs) averaging more than 60 per hour received a single 150-mg intravenous dose of pirmenol. Plasma pirmenol concentration declined biexponentially following the infusion and was analyzed according to a two-compartment open model. Following an erratic distribution phase, the terminal elimination half-life ranged from 4.2 to 16.9 hours, with a geometric mean of 7.6 hours. Total body clearance averaged 164 +/- 58 ml/min, and the mean volume of distribution was 1.45 +/- 0.38 liter/kg. Renal clearance averaged 46.6 +/- 21.2 ml/min, representing 30 +/- 10 per cent of total body clearance. Excretion of unchanged drug in the urine averaged 31.8 +/- 8 per cent of the dose. Renal clearance and elimination half-life were correlated (r = -0.61, P less than 0.05). Eight of the 12 patients achieved greater than 95 per cent suppression of PVCs with a duration between 20 minutes and 23 hours. These favorable pharmacokinetics indicate that pirmenol may be a useful addition to the therapy of ventricular arrhythmias.

Adult↗
PubMedDate not supplied

Flecainide: a new prototype antiarrhythmic agent.

Flecainide acetate is the first class IC antiarrhythmic agent marketed in the United States. In vitro, animal and human studies have shown that the drug markedly prolongs conduction and has minimal effect on repolarization. Efficacy trials have shown flecainide to be effective in a wide range of ventricular and selected atrial arrhythmias. The drug is generally well tolerated, although minor adverse effects are common. These generally are related to the central nervous system and respond to a reduction in dosage. Like other antiarrhythmic agents, flecainide may demonstrate proarrhythmic effects. It is excreted in the urine as the parent compound and inactive metabolites. The elimination half-life ranges from 12-27 hours in patients with normal renal function, allowing convenient dosing regimens of 100-200 mg twice daily in most patients. Flecainide has the potential for widespread use.

Administration, Oral↗