Studies on tritum-labeled digoxin: tissue, blood and urine determinations.

During the last 40 years extensive investigations have been reported on various aspects of the metabolism of cardiac glycosides. A detailed review describing the cellular basis of cardiac glycoside action has been reported by Hajdu and Leonard (1). One prime difficulty encountered in determining the metabolic fate of cardiac glycosides is in establishing a reliable and sensitive method for determining tissue, blood and urine levels of the glycosides as well as their derivatives in jian and in experimental animals. The minute amounts present in blood, urine and tissues after oral or parenteral administration require extremely sensitive assay methods. Digitalis glycosides have been studied by utilizing bioassay (2-9), colorimetric (10-14), radioisotopic (15-17), and polarographic techniques (18, 19). The behavior and fate of digitoxin in experimental animals and in man have been reviewed by Friedman, St. George and Bine (20). In Friedman's laboratory, bioassay techniques using embryonic duck hearts have detected 0.1 K.g of digitoxin per ml of serum of humans who received 1.2 mg digitoxin intravenously (21). The method consists of the observation of cardiac irregularities in embryonic duck hearts immersed in test fluids (8, 22). This group has reported reproducible results in studies of experimental animals and humans (8, 20, 22-30). Digitoxin labeled with carbon14 has been shown to be an excellent tool for appraising the behavior and fate of the glycoside (15-17, 31-38). Studies utilizing carbon14 digitoxin have included the fixation of cardioactive glycosides by isolated hearts (15); the tissue distribution and excretion in digitalis-sensitive and digitalis-resistant animals (16);