The renal excretion of digitoxin in the normal subject after single and continuous administration of the drug.

By employing the embryonic duck heart method to assay digitoxin quantitatively in extracts of human urine, it was found that, contrary to previous opinion, a large percentage of ingested or in-injected digitoxin is excreted via the kidney in a physiologically active state. Approximately 40 per cent of a digitalizing dose (1.2 mg.) is excreted over a period of 12 to 24 days. The average rate of renal excretion in theoretically digitalized normal young individuals was found to vary from 30 to 50,g. of digitoxin per day, while those showing signs or symptoms of overdosage exereted significantly greater amounts of digitoxin. IT HAS BEEN impossible heretofore to measure quantitatively the renal excretion of any digitalis glycoside after its administration to man. Hatcher and Eggleston,' in 1919, attempted by means of an indirect measurement to determine the renal excretion of ouabain, amorphous strophanthin and digi-toxin in the rat and cat after the administration of tremendous amounts of the various gly-cosides. They concluded that relatively little of any glycoside studied was excreted in the urine after its oral administration. Clinically, it has been assumed that a person of average weight either destroys or excretes in some manner 0.1 to 0.2 Gm. of digitalis or 0.1 to 0.2 mg. of digitoxin per day. Recently, employing the embryonic duck heart method,2 we were able to determine the renal excretion of digitoxin in the rat.3 It was found that less than 5 per cent of a parenterally administered dose of digitoxin was excreted by the kidney within 24 hours after its administration. None could be found in the urine after the first 24 hours. Preliminary studies on man,4' however, indicated that digitoxin was not only present in the first day's urine, but Works. 749 also in later collections. This suggested that the excretion of digitoxin in man differed quantitatively from that observed in the rat. In the present report quantitative studies were made concerning the extent and duration of renal excretion in normal individuals after various modes of administration. METHODS Ill order to determine the digitoxin content of human urine, chemical extraction of a fixed quantity (200 cc.) of a total daily urine volume was (lone. The final extract was dissolved in Tyrode's solution and at least six embryonic (luck hearts were ad(led to this solution. The average time at which the "digitalis effect"2 occurred in the hearts was noted and, by comparison with values obtained …