Disposition of beta-methyldigoxin in man.

The time course of radioactivity in plasma and the excretion in urine and faeces over 7 days were determined in 12 healthy subjects after single oral and intravenous doses of a solution of 3H-beta-methyldigoxin. 62.2 +/- 2.1 and 29.0 +/- 5.2 per cent of the dose were excreted in urine and faeces, respectively, within 7 days of intravenous administration, compared with 55.2 +/- 2.8 and 28.6 +/- 5.7 per cent after oral administration. This indicates almost complete absorption of the glycoside when given in solution. 12 hours after its administration a pseudo-distribution equilibrium was reached and the average half life of tritiated compounds was 1.3 days. By 48 - 96 hours after treatment the average half life was 2.8 days. O-demethylation was revealed as the main metabolic degradation step in man. The rate of Demethylation was higher after oral than i.v. administration. Thus, only 31% of the radioactivity excreted in the urine consisted of unchanged beta-methyl-digoxin after oral administration compared to 51% after i.v. dosing. Only traces of bis- and monoglycosides were excreted in urine, but there were considerable amounts in faeces, where they accounted for more than 35% of the total excretion. Up to 40% of the radioactivity in plasma and urine consisted of polar conjugates during the first 12 hours after administration of beta-methyldigoxin. The mono- and bisglycosides were identified as the main products of conjugation. During the 7 days approximately 15% of the administered dose was metabolized by splitting off glycosidic bonds and conjugation to polar compounds.