1. [12α-3H]Digoxin and polyethylene glycol (nonabsorbable marker) dissolved in water were administered orally to five healthy subjects.
2. The ratio between the amount of radioactivity/mg of polyethylene glycol in gastro-intestinal aspirates and that of the test solution demonstrated that 40–60% of the radioactivity administered was absorbed in the stomach and the proximal part of the small intestine.
3. Evidence for additional possible uptake in the lower gut was obtained by intrajejunal instillation of [3H]digoxin into the jejunum of one subject.
4. The recovery of radioactivity in the urine ranged between 43 and 62%. The total absorption might exceed the amount excreted in the urine since there was evidence of biliary excretion of radioactivity.
5. Some of the radioactivity in gastrointestinal aspirates was attached to digoxigenin and its derivatives with one or two digitoxoside groups. Studies in vitro indicated that these compounds were produced during the exposure of radioactive digoxin to the acid gastric content.
6. [12α-3H]Digoxigenin was administered orally to one subject. The uptake of radioactivity was essentially the same as that after the administration of [3H]digoxin.
7. It was concluded that the absorption of radioactivity following the administration of labelled digoxin reflects the combined uptake of the glycoside and metabolites.
8. The uptake of the intact glycoside was calculated to be approx. 50%.