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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 292, Issue 1, pp 87–92 | Cite as

Effects of pretreatment with spironolactone on pharmacokinetics of 4‴-methyldigoxin in man

  • U. Abshagen
  • H. Rennekamp
  • J. Kuhlmann
Article

Summary

Pharmacokinetics of 3H-4‴-methyldigoxin (md) were studied in three paired experiments with and without pretreatment with spironolactone (7 mg/kg/day for 7 days) and in one additional test person after pretreatment only. The results were compared with controls after oral (n=6) and intravenous (n=6) administration of md. In addition the biliary excretion of md and its metabolites was investigated in biliary fistula patients with and without pretreatment with spironolactone.

After pretreatment of normal persons maximum plasma levels of tritium were approximately 35% lower and they were reached on average 60 min after oral administration as compared with approximately 15 min without pretreatment. Already 12 hrs after oral administration the plasma concentrations, with and without pretreatment, no longer differed and the biological half lives of radioactivity in plasma were equal.

With or without pretreatment, the cumulative excretion of tritium in urine and faeces was nearly identical in the paired experiments within 7 days. It was in the range of the controls which eliminated 55.2±2.8 and 28.6±5.7% of the dose in urine and faeces, respectively, after oral, and 62.2±2.1 and 28.9±5.2%, respectively, after i.v. administration. Accordingly after pretreatment the radioactivity excreted in bile within 48 hrs (14.9% of the dose) did not differ from controls. Examination of the composition of labelled compounds excreted in urine and bile revealed no significant alterations in the metabolic degradation of md under the influence of spironolactone. Thus the profound effects of spironolactone upon pharmacokinetics of md previously observed in rats are without any significance for human conditions.

Key words

Spironolactone 4‴-Methyldigoxin Half life in plasma Biliary, faecal and renal excretion Metabolism Clinical pharmacology 

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Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • U. Abshagen
    • 1
  • H. Rennekamp
    • 1
  • J. Kuhlmann
    • 1
  1. 1.Institut für klinische Pharmakologie und Medizinische Klinik und PoliklinikKlinikum der Freien Universität BerlinBerlin 45

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