Administration of tritiated digoxin with and without a loading dose. A metabolic study.

IN 1919, Pardee attempted to assess the daily maintenance requirements of digitalis.1 He administered digitalis to patients in small repetitive doses until toxicity occurred. Digitalis was then withheld for some days and the patients were again given digitalis until toxicity developed. He calculated that the amount required to achieve toxicity the second time minus that required the first time divided by the number of days was equal to the daily elimination of digitalis. Thus, a fixed daily rate of excretion was assumed in these calculations. However, in 1923, Gold2 demonstrated that animals did not eliminate a fixed quantity of digitalis in a unit of time, but rather excreted a fraction of the amount present. He then proceeded to confirm the lack of a fixed rate of excretion in man. In 1929, Gold and DeGraff3 stated "that digitalis cumulation tends to be a self-limiting process; that a given dose of digitalis may show evidence of cumulation at first and later cease to show cumulation when the same daily dose is continued.... In other words, as the quantity of digitalis in the body increases, the amount eliminated daily also increases until the quantity eliminated equals the daily dose; then further cumulation no longer occurs. The intensity of digitalis action present at the time that cumulation ceases depends on the size of