Summary
With regard to the metabolism of digitalis glycosides, recent experiments show that cleavage of the sugar residues in the liver is not simple hydrolysis but an oxidative process which is catalyzed by the cytochrome P 450 system.
The enzymatic 12 β-hydroxylation of digitoxin to digoxin is quantitatively neglisible in man.
The pattern of digitoxin and digoxin metabolites, which is found to be fairly inhomogeneous in various studies, considerably depends on the different experimental designs, for instance, on the mode of administration. The relatively low recovery of the glycosides and their metabolites in urine and (if investigated) also in feces makes the evaluation of metabolism and its magnitude more difficult. Approximately, digitoxin is metabolized to 20–50%, digoxin to 5–50%.
With respect to strophanthus glycosides, an insufficient recovery was also noted in most of the studies. In contrast to ouabain, cymarin and orally given k-strophanthoside were found to be highly metabolized in urine. Intravenously injected k-strophanthoside was excreted in urine mainly as unchanged drug.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Doherty JE (1968) The clinical pharmacology of digitalis glycosides: A review. Am J Med Sci 255: 382 – 412
Doherty JE (1973) Digoxin: present knowledge of pharmacokinetics and pharmacodynamics. In: Storstein O (ed) Symposium on Digitalis. Gyldendal Norsk Forlag, Oslo, p 419
Gault MH, Longerich LL, Loo JCK, Ko PTH, Fine A, Vasder SC, Dawe MA (1984) Digoxin biotransformation. Clin Pharmacol Ther 35: 74 – 82
Herrmann I, Repke K (1963) Über die Biotransformation von Digitoxin und Digitoxigenin in der menschlichen Leber. Monatsber Dtsch Akad Wissenschaften Berlin 5: 140 – 143
Kuhlmann J, Abshagen U, Rietbrock N (1974) Pharmacokinetics and metabolism of digoxigeninmonodigitoxoside in man. Eur J Clin Pharmacol 7: 87 – 94
Kuhlmann J (1981) Metabolismus von Digitoxin. In: Digitâlistherapie bei Herzinsuffizienz, S. 9. Intern Symposium in Taormina, 8.-12.6.1980. -Urban + Schwarzenberg Verlag, Berlin Wien Baltimore
Lukas DS (1973) Pharmacokinetics andmetnbolism’df digitoxin in man. In: Symposium on digitalis. Storstein O (ed). Oslo: Gyldendal Norsk Forlag, pp 84 – 102
Lukas DS (1978) Studies of the metabolism of digoxin and digitoxin using double isotope dilution derivative methods. In: Bodem G, Dengler HJ (eds) Cardiac glycosides, Part I, International Boehringer Mannheim Symposia. Springer-Verlag, Berlin Heidelberg New York, p 36
Magnussen JO, Bergdahl B, Bogenstoft C, Jonsson UE, Tekenbergs L (1982) Excretion of digoxin and its metabolites in urine after a single oral dose in healthy subjects. Biopharm & Drug Disp 3: 21–118
Magnussen JO (1983) Metabolism of digoxin after oral and intrajejunal administration. Br J Clin Pharmac 16: 741 – 742
Marcus FI, Burkhalter L, Cuccia C, Pavlovich J, Kapadia GG (1966) Administration of tritiated digoxin with and without a loading dose. A metabolic study. Circulation 24: 865–874
Okita GT, Talso PJ, Curry JH, Smith FD, Geiling EMK (1955) Metabolic fate of radioactive digitoxin in human subjects. J Pharmacol 115: 371 – 379
Okita GT (1964) Metabolism of radioactive cardiac glycosides. Pharmacologist 6: 45
Repke K (1959) Über Spaltung und Hydroxylierung von Digitoxin bei der Ratte. Naunyn Schmiedeberg’s Arch Exp Path Pharmakol 237: 34 – 48
Repke K (1966) Biochemie und Klinik der Digitalis. Internist 7: 418 – 426
Repke K (1970) Stoffwechsel und Wirkung von Digitalisglykosiden. Ost Apoth Ztg 24: 515
Rietbrock N, Vöhringer HF, Kuhlmann J (1977) Der Metabolismus herzwirksamer Glykoside. Herz/ Kreisl 9: 825 – 832
Rietbrock N, Woodcock BG (1981) Pharmacokinetics of digoxin and derivatives. In: Greeff K (Hrsg) Cardiac Glycosides. Handbuch der experimentellen Pharmakologie, Vol 56 /11. Springer-Verlag, Berlin Heidelberg New York
Rojsathaporn K (1982) Zur Pharmakokinetik der Strophanthusglykoside beim Menschen. Inaugural-Dissertation, Düsseldorf
Schmoldt A, Benthe HF, Haberland G (1975) Digitoxin metabolism by rat liver microsomes. Biochem Pharmacol 24: 1639 – 1641
Schmoldt A (1984) Untersuchungen zum Metabolismus der Digitalisglykoside. Beiträge zur gerichtl Medizin 42: 95 – 101
Selden R, Margolies N, Smith TW (1974) Renal and gastrointestinal excretion of ouabain in dog and man. J Pharmacol Exp Ther 188: 615 – 623
Storstein L (1977) Studies on digitalis. VIII. Digitoxin metabolism on a maintenance regimen and after a single dose. Clin Pharmacol Ther 21: 125 – 140
Storstein L (1981) Pharmacokinetics of digitoxin. In: Cardiac Glycosides. Handbook of Experimental Pharmacology, Vol 56/II, S 3, Greeff K (ed), Springer-Verlag, Berlin Heidelberg New York
Vöhringer HF, Rietbrock N (1974) Metabolism and excretion of digitoxin in man. Clin Pharmacol Ther 16: 796 – 806
Vöhringer HF, Rietbrock N (1978) Pharmacokinetics and Metabolism of Digitoxin in the human. In: Bodem, G, Dengler, HJ (eds) Cardiac Glycosides, Part I. International Boehringer Mannheim Symposia. Springer-Verlag, Berlin Heidelberg New York, p 64
Wirth KE, Frölich JC, Hollefield JW, Falkner FC, Sweetman BS, Oates JA (1976) Metabolism of digitoxin in man and its modification by spironolactone. Eur J Clin Pharmacol 9: 345 – 354
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1986 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Wirth, K.E. (1986). Relevant metabolism of cardiac glycosides. In: Erdmann, E., Greef, K., Skou, J.C. (eds) Cardiac Glycosides 1785–1985. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-662-11292-2_33
Download citation
DOI: https://doi.org/10.1007/978-3-662-11292-2_33
Publisher Name: Steinkopff, Heidelberg
Print ISBN: 978-3-662-11294-6
Online ISBN: 978-3-662-11292-2
eBook Packages: Springer Book Archive