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


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 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abshagen, U.: Effects of pretreatment with spironolactone on pharmacokinetics of 4‴-methyldigoxin in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 91–100 (1973)Google Scholar
  2. Abshagen, U., Rennekamp, H.: Influence of chronic treatment with spironolactone on its own pharmacokinetics and on the liver function in normals and cirrhotics. International Symposium on Diuretics in Research and Clinics, Bürgenstock 1975. Abstracts: Ed. W. Siegenthaler, pp. 76–79. Karlsruhe: Verlag G. Braun 1975Google Scholar
  3. Buck, S. H., Lage, G. L.: Possible mechanism of the prevention of digitoxin toxicity by spironolactone in the mouse. Arch. int. Pharmacodyn. 189, 192–197 (1971)Google Scholar
  4. Castle, M. C., Lage, G. L.: Effect of pretreatment with spironolactone, phenobarbital or β-diethylaminoethyl diphenylpropyl-acetate (SKF 525-A) on tritium levels in blood, heart and liver of rats at various times after administration of (3H) digitoxin. Biochem. Pharmacol. 21, 1449–1455 (1972)Google Scholar
  5. Castle, M. C., Lage, G. L.: Enhanced biliary excretion of digitoxin following spironolactone as it relates to the prevention of digitoxin toxicity. Res. Commun. Chem. Path. Pharmacol. 5, 99–108 (1973a)Google Scholar
  6. Castle, M. C., Lage, G. L.: 3H-Digitoxin and its metabolites following spironolactone pretreatment of rats. Res. Commun. Chem. Path. Pharmacol. 6, 601–612 (1973b)Google Scholar
  7. Castle, M. C., Lage, G. L.: Cleavage by β-glucuronidase of the water-soluble metabolites of digitoxin excreted in the bile of control and spironolactone-pretreated rats. Toxicol. appl. Pharmacol. 27, 641–647 (1974)Google Scholar
  8. Kaiser, F.: Die papierchromatographische Trennung von Herzgiftglykosiden. Chem. Ber. 88, 556–563 (1955)Google Scholar
  9. Krämer, K.-D., Ghabussi, P., Hochrein, H.: Klinische Prüfung der subtoxischen Vollwirk- und Erhaltungsdosis von Digoxin unter dem Einfluß von Spironolaktone. Arneimittel-Forsch. (Drug Res.) 23, 508–511 (1973a)Google Scholar
  10. Krämer, K.-D., Vogt, W., Ghabussi, P., Hochrein, H.: Therapeutischer Wert des Aldosteron-Autagonisten Kalium-Canrenoat bei der Digitalisintoxikation. Med. Welt 24, 462–467 (1973b)Google Scholar
  11. Rietbrock, N., Abshagen, U.: Stoffwechsel und Pharmakokinetik der Lanataglykoside beim Menschen. Dtsch. med. Wschr. 98, 117–122 (1973)Google Scholar
  12. Sadée, W., Dagcioglu, M., Riegelman, S.: A fluorimetric microassay for spironolactone and its metabolites in biological fluids. J. pharm. Sci. 61, 1126–1129 (1972)Google Scholar
  13. Sadée, W., Dagcioglu, M., Schröder, R.: Pharmacokinetics of spironolactone, canrenone and canrenoate-K in humans. J. Pharmacol. exp. Ther. 185, 686–695 (1973)Google Scholar
  14. Sadée, W., Abshagen, U., Finn, C., Rietbrock, N.: Conversion of spironolactone to canrenone and disposition kinetics of spironolactone and canrenoate-potassium in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 283, 303–318 (1974a)Google Scholar
  15. Sadée, W., Schröder, R., Leitner, E. v., Dagcioglu, M.: Multiple dose kinetics of spironolactone and canrenoate-potassium in cardiac and hepatic failure. Europ. J. clin. Pharmacol. 7, 195–200 (1974b)Google Scholar
  16. Selye, H., Jelinek, J., Krajny, M.: Prevention of digitoxin poisoning by various steroids. J. pharm. Sci. 58, 1055–1059 (1969a)Google Scholar
  17. Selye, H., Krajny, M., Savoie, L.: Digitoxin poisoning: prevention by spironolactone. Science 164, 842–843 (1969b)Google Scholar
  18. Selye, H., Mécs, I., Tamura, T.: Effect of spironolactone and norbolethone on the toxicity of digitalis compounds in the rat. Brit. J. Pharmacol. 37, 485–488 (1969c)Google Scholar
  19. Wirth, K. E., Frölich, J. C.: Effect of spironolactone on excretion of 3H-digoxin and its metabolites in rats. Europ. J. Pharmacol. 29, 43–51 (1974)Google Scholar

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

Personalised recommendations