Metabolism and excretion of 3H-digitoxin in the rat

After oral administration of 25 μg/kg ³H-labelled digitoxin (sp. act. 26.2 mCi/mg) to female rats, the total radioactivity in blood and in urine was eliminated with a half-life time of 2 and 1.7 days, respectively. The fecal elimination half-life time had a. biphasic course. The chloroform-soluble and chloroform-insoluble metabolites excreted in urine and feces were determined in order to explain the much shorter half-life time of 0.4 days in feces during the early phase of elimination. In the feces, 45 per cent of the dose excreted within 5 days consisted of chloroform-soluble substances. In this fraction, the main excretion product was digoxigenin-bis-digitoxoside (20 per cent), whereas the percentages of the other glycosides, after the last collection period, amounted to significantly less: 9% digitoxin, 9% digoxin. 5% digitoxigenin-bis-digitoxoside, and 2% digitoxigenin-mono-digitoxoside. The Chromatographic analysis of the chloroform-insoluble fraction, which accounted for 15 per cent of the dose. revealed a conjugation of glucuronic and sulfuric acid with digoxin, and digoxin, 5% digitoxigenin-bis-digitoxosidc. and 2% digitoxigenin-mono-digitoxoside. The contrast, sulfuric acid alone was the main conjugation partner of 3-epi-digitoxigenin. In urine, 4.6 per cent of the administered radioactivity was represented by digoxin, 2 per cent by digitoxin, 1 per cent by digoxigenin-bis-digitoxoside, and 1.4 per cent by polar metabolites. Only traces of digitoxigenin-bis-digitoxoside cind digoxigenin-mono-digitoxoside were detected. The much shorter half-life time of the eliminated radioactivity in feces seems to be due to the higher portion of poorly reabsorbed conjugation products and digoxigeninbis-digitoxoside.