Excretion of digoxin and its metabolites in urine after a single oral dose in healthy subjects.

The 3-day urinary excretion of digoxin, its conjugated and unconjugated hydrolytic metabolites and dihydrodigoxin, was studied in 8 healthy men after oral administration of tritiated digoxin. Analysis was performed by high pressure liquid chromatography (HPLC). The total radioactivity corresponded to 45.4 +/- 2.0 per cent (mean +/- S.E.M.) of the dose. By HPLC 42.4 +/- 2.7 per cent was recovered before and 44.0 +/- 2.7 per cent after deconjugation of the samples. Digoxin and dihydrodigoxin constituted 40.3 +/- 2.9 per cent; of this 0.7 +/- 0.4 per cent was dihydrodigoxin. The sum of the hydrolytic metabolites was 2.1 +/- 0.3 per cent before and 3.4 +/- 0.5 per cent after deconjugation. No correlation was found between gastric pH and the production of hydrolytic metabolites. The relative amount of these metabolites was maximal (mean 13.4 per cent of the excretion) in the 4-8 h sampling period. During the first 8 h an average of 8.6 per cent of the radioactivity was not recovered by HPLC. The metabolism of digoxin as judged by urinary excretion was limited and showed great variation during the early hours after treatment. The excretion of unchanged digoxin in some individuals constituted as little as 60 per cent over the first 12 h after dosing.