Digoxigenin biotransformation.

Two healthy subjects took 3H-digoxigenin-12 alpha and unlabeled digoxigenin. Metabolites were assayed by high-pressure liquid chromatography (HPLC) in serum and urine. Of the tritium activity in the serum at 30 min, less than 26% chromatographed with digoxigenin; the rest chromatographed as metabolites, most of which were polar. The main polar metabolites identified were glucuronides of 3-epidigoxigenin. An important route of biotransformation to polar metabolites appears to be from 3 beta-digoxigenin through 3-keto-digoxigenin to 3-epidigoxigenin. Several HPLC peaks remain unidentified. There was extensive cross reactivity between metabolites and antisera to digoxin. The digoxigenin route of digoxin biotransformation to polar metabolites may be important in some patients receiving digoxin and such metabolites could contribute an important fraction to the serum digoxin concentration measured by radioimmunoassay.