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Biomedical subjects

F I Marcus

Publications and source records attributed to F I Marcus.

At least 91 records · Page 5Linked to original sources
PubMed1986

Effects of antiarrhythmic drugs on the chronic pacing threshold and the endocardial R wave amplitude in the conscious dog.

To determine the effects of antiarrhythmic drugs on the chronic pacing threshold and the endocardial R wave amplitude, we tested seven drugs (representative of Vaughn Williams' antiarrhythmic class-I-IV) on four to six dogs after the implanted ventricular endocardial bipolar leads had reached chronic stable thresholds. The seven antiarrhythmic drugs tested were procainamide (oral [p.o.] and intravenous [IV], class IA), lidocaine (IV, class IB), tocainide (p.o., class IB), flecainide (p.o. and IV, class IC), propranolol (p.o. and IV, class II), amiodarone (p.o. and IV, class III), and verapamil (p.o. and IV, class IC), propranolol (p.o. and IV, class II), amiodarone (p.o. and IV, class III), and verapamil (p.o. and IV, class IV). The drugs were administered in sufficient doses to achieve plasma levels associated with antiarrhythmic efficacy in humans. All oral drugs were given for sufficient time to achieve expected steady state levels. The pacing thresholds, both voltage and current, and the endocardial R wave amplitude were measured in the conscious dog with a Medtronic pacing system analyzer at a pulse width of 0.1, 0.5, 1.0, and 2.0 ms at intervals following IV or p.o. administration of each antiarrhythmic drug. We found that there were no significant effects of the tested seven antiarrhythmic drugs on the chronic pacing threshold and the endocardial R wave amplitude at any of the pulse widths. We conclude that in the healthy dog antiarrhythmic drugs do not alter the pacing threshold and the endocardial R wave amplitude.

Animals↗
PubMed1985

Assessment of the potential pharmacokinetic interaction between digoxin and ethmozine.

The potential for a pharmacokinetic interaction between the investigational antiarrhythmic drug ethmozine (moricizine HCl, the generic name that is infrequently used in existing literature) and digoxin was evaluated in nine healthy male adults. Serum and urinary digoxin concentrations were measured by radioimmunoassay following intravenous digoxin administration before and during steady-state ethmozine dosing. Plasma ethmozine levels following a single oral dose were measured before and after a single intravenous dose of digoxin. A mean elimination half-life of 45.6 hours was determined for digoxin alone, compared to 43.1 hours in combination with ethmozine. Average values for digoxin systemic clearance, apparent volume of distribution, and renal clearance were 2.87 mL/min/kg, 11.3 L/kg, and 2.44 mL/min/kg, respectively for digoxin alone, compared to 3.01 mL/min/kg, 11.3 L/kg, and 2.64 mL/min/kg, respectively for digoxin with ethmozine. A mean half-life of 2.0 hours was determined for ethmozine alone, compared with 1.8 hours following a single intravenous dose of digoxin. No change was observed in the oral pharmacokinetics of ethmozine following a single intravenous dose of digoxin, as indicated by the area under the plasma concentration versus time curve, Cmax or Tmax. These findings suggest that no pharmacokinetic interaction occurs when single intravenous doses of digoxin are co-administered with multiple oral doses of ethmozine.

Adult↗
PubMed1985

Bioavailability of the bis- and monodigitoxosides of digitoxigenin.

The pharmacokinetic behavior of digitoxigenin is affected by the number of glycosides present. This study was conducted to compare the bioavailabilities of the bis- and monodigitoxosides of digitoxigenin in man. Intravenous and oral doses of the two drugs were administered to six normal volunteers. Blood samples were collected up to 28 days after each dose, and assayed for the specific drug administered and for total radioassayable drug. Both drugs were virtually completely absorbed, based on serum concentrations of administered drug plus metabolites. However, the mean bioavailability of unchanged bisdigitoxoside was only 56.3% indicating that substantial metabolism occurred prior to entry into the systemic circulation. Monodigitoxoside was virtually completely metabolized prior to entry into the systemic circulation.

Administration, Oral↗
PubMed1985

Pharmacokinetic interactions between digoxin and other drugs.

Drug interactions with digoxin are important because of this agent's narrow therapeutic index. Among the drugs that can decrease digoxin bioavailability are cholestyramine, antacid gels, kaolin-pectate, certain antimicrobial drugs and cancer chemotherapeutic agents. In selected patients, antibiotics may enhance digoxin bioavailability by eliminating intestinal flora that metabolize digoxin. Antiarrhythmic drugs, such as quinidine and amiodarone, can markedly increase steady state serum digoxin levels. Certain calcium channel blocking drugs, particularly verapamil, have a similar effect. Potassium-sparing diuretic drugs, such as spironolactone, can alter digoxin pharmacokinetics. Indomethacin may decrease renal excretion of digoxin in preterm infants. Finally, rifampin, an antibiotic used in the treatment of tuberculosis, may lower steady state serum digoxin levels in patients with severe renal disease. Physicians must maintain constant vigilance whenever medications are added to or withdrawn from a therapeutic regimen that includes digoxin.

Antacids↗
PubMed1984

Prognosis of patients with diabetes mellitus after acute myocardial infarction.

Sixty patients with diabetes mellitus who survived the coronary care unit phase of acute myocardial infarction (AMI) were followed an average of 19 months and the prognosis of diabetic patients was compared with that of 719 nondiabetic patients. The mortality rate was 25% in diabetic patients and 8% in nondiabetic patients. These patients had been entered in a Multicenter Postinfarction Program, where analysis of the total data base showed 4 significant prognostic factors: cardiac symptoms before AMI, pulmonary rales when the patient was in the coronary care unit, more than 10 ventricular premature complexes per hour recorded on Holter monitor just before discharge, and a radionuclide ejection fraction of less than 40%. Of these 4 factors, only cardiac symptoms before AMI was significantly more common in diabetic patients (57% in diabetic vs 36% in nondiabetic patients). When each of these 4 factors was stratified for severity, the mortality rate was always higher in diabetic patients. The data were examined to determine other factors in diabetic patients who died. Pulmonary rales was significantly more common in diabetic patients who died (6% in survivors vs 42% in patients who died). In a multivariate analysis of both diabetic and nondiabetic patients, 5 factors were significant determinants of prognosis. They are, in order of entry into the model, rales (p less than 0.001), ejection fraction less than 40% (p less than 0.001), diabetes (p less than 0.001), symptoms before AMI (p = 0.009), and more than 10 ventricular premature complexes per hour (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Complications↗
PubMed1984

Kinetics of digitoxin and the bis- and monodigitoxosides of digitoxigenin in normal subjects.

The kinetics of digitoxin and two of its metabolites, the bis- and monodigitoxosides of digitoxigenin, were determined in six normal subjects. Mean t 1/2s and total body clearances were 134.4, 15.4, and 0.59 hr and 2.66, 27.3, and 1071 ml/min. Mean renal clearance of the monodigitoxoside was more rapid (7.24 ml/min) than those of digitoxin (0.81 ml/min) or the bisdigitoxoside (0.94 ml/min). The volumes of distribution were of the same order, 0.45 l/kg for digitoxin, 0.57 l/kg for the bisdigitoxoside, and 0.83 l/kg for the monodigitoxoside. The short t 1/2 of monodigitoxoside would make it unsuitable for clinical use, but the bisdigitoxoside of digitoxigenin has a t 1/2 of an intermediate length and may have significant therapeutic advantages.

Adult↗
PubMed1984

Kinetics of digitoxin and the bis- and monodigitoxosides of digitoxigenin in renal insufficiency.

The kinetics of digitoxin and two of its major metabolites, the bis- and monodigitoxosides of digitoxigenin, were determined in six subjects with renal insufficiency and compared to those in six age- and sex-matched normal control subjects. No significant differences between the two groups were found in elimination t 1/2, total body clearance, or volume of distribution. Average renal clearances of all three drugs were reduced in subjects with renal failure, but the differences were significant only in the case of digitoxin. The bis-digitoxoside of digitoxigenin has kinetic properties that offer clinical advantages.

Acute Kidney Injury↗
PubMed1984

Pharmacokinetics and bioavailability of digitoxin by a specific assay.

The pharmacokinetics and bioavailability of digitoxin were examined in six normal human subjects using an assay that separates digitoxin from its metabolites. After intravenous administration, the mean systemic clearance was 2.44 ml/min; the volume of distribution was 0.47 l/kg; and the elimination half-life was 6.5 days. After oral administration, the elimination half-life was 5.8 days. The bioavailability was 81.5% using the specific assay. Using a non-specific, direct serum digitoxin radioimmunoassay the bioavailability was 98.0%. Assay of aqueous fractions from extracted serum samples indicated higher levels of water-soluble metabolites following oral compared to intravenous digitoxin administration. These findings suggest that previously reported values for digitoxin bioavailability using non-specific methods may be falsely elevated due to the presence of digitoxin metabolites in serum.

Adult↗
PubMed1984

Prognosis after myocardial infarction.

There is 10-20 percent mortality in the first two years after hospital discharge from a myocardial infarction. Patient management would be facilitated if one could stratify patients into those who have a low, medium or high risk of death within the first two years following infarction. Towards achieving this end a multicenter study was designed. 866 patients were enrolled over a two-year period from four widely separated geographic centers in the United States. Criteria for enrollment included definite acute myocardial infarction and age less than 70 years. 452 clinical variables were obtained from each patient and entered into a central computer file. Special studies obtained just prior to discharge included a 24-hour computer analyzed Holter recording and a radionuclide ejection fraction. 70 percent of the patients had a low-level predischarge treadmill activity test. Before the study a hypothesis was generated and tested prospectively. This was as follows: there are three clinical risk variables that have independent influence on survival. They are: ejection fraction less than 40 percent, ventricular ectopic depolarization frequency greater than 10 per hour, and the presence of angina pectoris before hospital discharge. The 22-month mortality was 11.6 percent (101 deaths). The variables which had the most significant association with cardiac mortality were those which reflected mechanical cardiac dysfunction either before or during acute hospitalization. The arrhythmia variable (VEDs) were less strongly associated with mortality than the mechanical parameters and the ischemia variable (angina pectoris prior to discharge) did not significantly discriminate between those who survived and died.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1983

Quantitation of digitoxin and the bis- and monodigitoxosides of digitoxigenin in serum.

A specific assay is described for measuring the concentration of digitoxin and the bis- and monoglycosides of digitoxigenin in serum. The procedure includes: (1) addition of a tracer amount of tritium labeled parent compound to the serum in order to measure percentage recovery; (2) solvent extraction to separate polar and non-polar metabolites; (3) reversed-phase thin-layer chromatography of the non-polar fraction to separate digoxigenins from digitoxigenins; (4) thin-layer chromatography to isolate digitoxin, and the bis- and monoglycosides of digitoxigenin; and (5) use of an 125I-radioimmunoassay to determine the concentration of the glycosides. Each of these three glycosides was administered intravenously to a normal subject, and the concentration of parent compound was measured in the serum at various times.

Adult↗