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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and metabolism of digoxigenin-mono-digitoxoside in man (1974)
    Springer
    European journal of clinical pharmacology 7 (1974), S. 87-94 
    Details
    ISSN: 1432-1041
    Keywords: Digoxigenin-mono-digitoxoside ; cardiac glycosides ; metabolism ; excretion ; polar conjugates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561320
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  • 2
    Electronic Resource
    Electronic Resource
    Disposition of β-methyldigoxin in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 105-114 
    Details
    ISSN: 1432-1041
    Keywords: Methyldigoxin ; excretion ; deep compartment ; O-demethylation ; glycosides ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course of radioactivity in plasma and the excretion in urine and faeces over 7 days were determined in 12 healthy subjects after single oral and intravenous doses of a solution of3H-β-methyldigoxin. 62.2±2.1 and 29.0±5.2 per cent of the dose were excreted in urine and faeces, respectively, within 7 days of intravenous administration, compared with 55.2±2.8 and 28.6±5.7 per cent after oral administration. This indicates almost complete absorption of the glycoside when given in solution. 12 hours after its administration a pseudo-distribution equilibrium was reached and the average half life of tritiated compounds was 1.3 days. By 48 – 96 hours after treatment the average half life was 2.8 days. O-demethylation was revealed as the main metabolic degradation step in man. The rate of Demethylation was higher after oral than i.v. administration. Thus, only 31% of the radioactivity excreted in the urine consisted of unchanged β-methyldigoxin after oral administration compared to 51% after i.v. dosing. Only traces of bis- and monoglycosides were excreted in urine, but there were considerable amounts in faeces, where they accounted for more than 35% of the total excretion. Up to 40% of the radioactivity in plasma and urine consisted of polar conjugates during the first 12 hours after administration of β-methyldigoxin. The mono- and bisglycosides were identified as the main products of conjugation. During the 7 days approximately 15% of the administered dose was metabolized by splitting off glycosidic bonds and conjugation to polar compounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614005
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    Paper (German National Licenses)
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