We evaluated a commercial (Clinical Assays, Inc.) 125I radioimmunoassay for digitoxin for use in measuring cardiac glycosides in serum, buffer, urine, and cerebrospinal-fluid samples. We also assessed interference of seven cardioactive metabolites of digitoxin, including digoxin, with the assay. The precision of the assay was adequate for all matrixes studied for glycoside concentrations less t...

Previous studies of digitalis glycoside metabolism and excretion have indicated that these compounds undergo a significant enterohepatic cycle in some species. It has been suggested that the existence of such a cycle in man contributes to the prolonged action of certain cardiac glycosides. Previous studies have demonstrated that cholestyramine binds digitoxin and digoxin in vitro and accelerate...

The tissue distribution and excretion of radioactive digitoxin and its metabolites were studied in normal rats and cats and in rats with dietary induced myocardial lesions. The prolonged cardiac and renal retention of digitoxin and its derivatives, associated with the persistence of these substances in the excreta of sensitive animals, supports the concept of storage as an explanation for the c...

Modulation of alternative pre-mRNA splicing is a potential approach to therapeutic targeting for a variety of human diseases. We investigated the mechanism by which digitoxin, a member of the cardiotonic steroid class of drugs, regulates alternative splicing. Transcriptome-wide analysis identified a large set of alternative splicing events that change after digitoxin treatment. Within and adjac...

Previous studies have demonstrated that considerable amounts of parenterally administered cardiac glycosides are excreted in the bile and reabsorbed across the intestinal mucosa in several species. It is currently believed that the more prolonged action of nonpolar digitalis glycosides is due to their retention and recycling in the enterohepatic circulation. This report describes studies carrie...

The renal excretion of digitoxin was studied in cardiac patients who were (1) decompensated and (2) compensated. It was found that the renal excretion of digitoxin was not changed in patients suffering from left ventricular failure alone but diminished considerably during the first 24 hours of decompensation in patients suffering from both right and left ventricular failure. Patients who were m...

Serum digitoxin levels were measured in 18 infants (under two years) and in 23 children (aged 2-13 years) receiving maintenance therapy. Digitalization was carried out because of heart failure in 17 infants and 13 children and for control of dysrhythmia in one infant and 10 children. Mean maintenance dosage for infants was 0.0042 plus or minus 0.0008 (sd) mg/kg/day and for children was 0.0031 p...

Cystic fibrosis (CF) is a fatal, autosomal, recessive genetic disease that is characterized by profound lung inflammation. The inflammatory process is believed to be caused by massive overproduction of the proinflammatory protein IL-8, and the high levels of IL-8 in the CF lung are therefore believed to be the central mechanism behind CF lung pathophysiology. We show here that digitoxin, at sub...

Laboratories performing analyses for serum cardiac glycosides are sometimes faced with the problem of distinguishing between digoxin and digitoxin in a specimen. The antibodies to the cardiac glycosides supplied with radioimmunoassay kits for these drugs have some measurable degree of cross reactivity. Therapeutic levels of digitoxin are approximately ten times greater than those of digoxin, an...

Laboratories performing analyses for serum cardiac glycosides are sometimes faced with the problem of distinguishing between digoxin and digitoxin in a specimen. The antibodies to the cardiac glycosides supplied with radioimmunoassay kits for these drugs have some measurable degree of cross reactivity. Therapeutic levels of digitoxin are approximately ten times greater than those of digoxin, an...