Summary
3H-digoxigenin-mono-digitoxoside 1 mg was swallowed by 6 healthy subjects. Maximum plasma levels of radioactivity were reached within 1–2 h; in two subjects there was a second peak at 8–12 h. No definite half lives could be determined because the falls in plasma activity were not exponential. 3.9–39% and 34.5–76.6% of the dose were eliminated in urine and faeces, respectively. 75–90% of the total radioactivity in plasma was CHCl3-insoluble, there was less of this fraction in urine, and the major portion in faceces was CHCl3-soluble. The CHCl3-insoluble fraction in urine was separated into 3 components by chromatography on an Al2O3-column and consisted mainly of conjugates of the monoglycoside and 3-epidigoxigenin. TLC-separation of the lipophilic fraction in urine also revealed unchanged monoglycoside and 3-epidigoxigenin, as well as traces of digoxigenin, 3-ketodigoxigenin and 2 unidentified, more polar metabolites. In faeces, the main excretion product was the unchanged compound, and traces of digoxigenin, 3-epidigoxigenin, 3-ketodigoxigenin and one of the more polar metabolites detected in urine. Two patients with surgical T-tube bile-duct drainage showed significantly greater biliary excretion after oral administration of the digoxigenin-mono-digitoxoside than after digoxin. Almost all the radioactivity excreted in bile was CHCl3-insoluble and the monoglycoside was shown to be the only conjugation partner present by incubation with arylsulfatase and β-glucuronidase. The results show that digoxigenin-mono-digitoxoside has such a rapid metabolic inactivation and biliary clearance in man that it is unlikely to be of any therapeutic value.
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This study was supported by the Deutsche Forschungsgemeinschaft.
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Kuhlmann, J., Abshagen, U. & Rietbrock, N. Pharmacokinetics and metabolism of digoxigenin-mono-digitoxoside in man. Eur J Clin Pharmacol 7, 87–94 (1974). https://doi.org/10.1007/BF00561320
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DOI: https://doi.org/10.1007/BF00561320