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Bioavailability and pharmacokinetics of β- methyldigoxin after multiple oral and intravenous doses

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Summary

To obtain true half lives, glycoside elimination from six healthy subjects was studied for 14 days after multiple intravenous doses or oral administration of a daily maintenance dose of β-methyldigoxin 0.3 mg. After oral or intravenous administration of β-methyldigoxin ceased, the plasma concentrations declined from the 14th to the 16th days with a half life of 1.7 days. From the 16th to the 20th day a change from a shorter to a longer half life of 2.8 and 2.9 days was observed. Similar half lives were found in urine: after the last dose the initial slope from the 14th to the 16th day had a half life of 1.8 days, and the terminal slope had one of 3.2 days. The results indicate release of the glycoside from slowly equilibrating tissues.

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References

  1. Beermann, B.: The gastrointestinal uptake of methyldigoxin-12α-3H in man. Europ. J. clin. Pharmacol.5 28–33 (1972)

    Google Scholar 

  2. Belz, G.G.: Plasma concentrations of intravenous β-methyldigoxin with and without oral charcoal. Klin. Wschr.52 749–750 (1974)

    Google Scholar 

  3. Bertler, A., Gustafson, A., Redfors, A.: Massive digoxin intoxication. Acta med. scand.194 245–249 (1973)

    Google Scholar 

  4. Blankart, R.: Zum Verhalten der Herzglykoside im menschlichen Organismus. Eine Übersicht am Beispiel des Digoxins und des Lanatosid C. Ther. Umsch.28 205–211 (1971)

    Google Scholar 

  5. Bloom, P.M., Nelp, W.B.: Relationship of the excretion of tritiated digoxin to renal function. Amer. J. med. Sci.251 133–144 (1966)

    Google Scholar 

  6. Bodem, G., Wirth, K., Gernand, E., Dengler, H.J.: Pharmacokinetics and metabolism of α-acetyldigoxin in man. Arch. int. Pharmacodyn.208 102–116 (1974)

    Google Scholar 

  7. Carbonin, P.U., Zecchi, P., Bellocci, F., Ruffa, S., Loperfido, F.: Turnover metabolico della metildigossina -H3, somministrata per via orale ed endovenosa nell'uomo normale. Abstract from the 32th Congress of the Italian Society of Cardiology 1971

  8. Dengler, H.J., Bodem, G., Wirth, K.: Pharmakokinetische Untersuchungen mit3H-Digoxin und3H-Lanatosid beim Menschen. Arzneimittel-Forsch.23 64–74 (1973)

    Google Scholar 

  9. Dettli, L.: Pharmakokinetische Grundlagen für die optimale Dosierung bei repetierter Applikation von Arzneimitteln. 1. Symposion für Klinische Pharmakologie, Berlin 1975 (eds. K.-W. v. Eickstedt, F. Gross), pp. 59–68. Stuttgart: Gustav Fischer Verlag 1975

    Google Scholar 

  10. Doherty, J,E., Perkins, W.H., Mitchell, G.K.: Tritiated digoxin studies in human subjects. Arch. intern. Med.108 531–539 (1961)

    Google Scholar 

  11. Doherty, J.E., Perkins, W.H.: Studies with tritiated digoxin in human subjects after intravenous administration. Amer. Heart J.63 528–356 (1962)

    Google Scholar 

  12. Doherty, J.E.: The clinical pharmacology of digitalis glycosides. A review. Amer. J. med. Sci.255 382–414 (1968)

    Google Scholar 

  13. Doherty, J.E., Flanigan, W.J., Patterson, R.M., Dalrymple, G.V.: The excretion of tritiated digoxin in normal human volunteers before and after unilateral nephrectomy. Circulation10 555–561 (1969)

    Google Scholar 

  14. Doluisio, J.T., Dittert, L.W.: Influence of repetitive dosing of tetracyclines on biologic half - life in serum. Clin. Pharmacol. Ther.10 690–701 (1969)

    Google Scholar 

  15. Ewy, G.A., Kapadia, G.G., Yao, L., Lullin, M., Marcus, F.I.: Digoxin metabolism in the elderly. Circulation39 449–453 (1969)

    Google Scholar 

  16. Ewy, G.A., Groves, B.M., Ball, M.F., Nimmo, L., Jackson, B., Marcus, F.: Digoxin metabolism in obesity. Circulation44 810–814 (1971)

    Google Scholar 

  17. Falch, D.: The influence of kidney function, body size and age on plasma concentration and urinary excretion of digoxin. Acta med. scand.194 251–256 (1973)

    Google Scholar 

  18. Garrett, E.R.: The clinical significance of pharmacokinetics. Symposion in Schloß Reinhartshausen am Rhein, 12.5.1969. In: Symposia medica Hoechst, (ed. H.J. Dengler), pp. 5–21. Stuttgart - New York: Schattauer Verlag 1970

    Google Scholar 

  19. König, E., Ohly, A.: Quantitative Eigenschaften eines neuen Herzglykosids. Med. Klin.65 296–299 (1970)

    Google Scholar 

  20. Kramer, P., Horenkamp, J., Willms, B., Scheler, F.: Das Kumulationsverhalten verschiedener Herzglykoside bei Anurie. Dtsch. med. Wschr.95 444–453 (1970)

    Google Scholar 

  21. Kramer, W.G., Lewis, R.P., Cobb, T.C., Forester, W.F., Visconti, J.A., Wanke, L.A., Boxenbaum, H.G., Reuning, R.H.: Pharmacokinetics of digoxin: Comparison of a two- and a three-compartment model in man. J. Pharmacokinet. Biopharmaceut.2 299–312 (1974)

    Google Scholar 

  22. Larbig, D., Scheler, F., Schmidt, H.-J., Betzien, G., Kaufmann, B.: Untersuchungen zur enteralen Resorption von β-Methyldigoxin. Klin. Wschr.49 604–607 (1971)

    Google Scholar 

  23. Larbig, D., Kochsiek, K.: Radioimmunchemische Bestimmung von Digoxin im menschlichen Serum. Klin. Wschr.49 1031–1032 (1971)

    Google Scholar 

  24. Larbig, D., Kochsiek, K.: Zur radioimmunchemischen Bestimmung von Digoxin und Digoxinderivaten. Dtsch. med. Wschr.97 1310–1312 (1972)

    Google Scholar 

  25. Larbig, D., Kochsiek, K., Schrader, Chr.: Klinische Aspekte der radioimmunchemischen Bestimmung der Serum-Digoxinkonzentration. Dtsch. med. Wschr.97 139–145 (1972)

    Google Scholar 

  26. Marcus, F.I., Kapadia, G.J., Kapadia, G.G.: The metabolism of digoxin in normal subjects. J. Pharmacol. exp. Ther.145 203–209 (1964)

    Google Scholar 

  27. Rennekamp, H., Rennekamp, Ch., Abshagen, U., v. Bergmann, K., Rietbrock, N.: Pharmacokinetic behaviour of 4‴-methyldigoxin in man. Naunyn-Schmiedeberg's Arch. Pharmacol.273 172–174 (1972)

    Google Scholar 

  28. Rietbrock, N., Abshagen, U.: Stoffwechsel und Pharmakokinetik der Lanataglykoside beim Menschen. Dtsch. med. Wschr.98 117–122 (1973)

    Google Scholar 

  29. Rietbrock, N., Abshagen, U., v. Bergmann, K., Rennekamp, H.: Disposition of β-methyldigoxin in man. Europ. J. clin. Pharmacol.9 105–114 (1975)

    Google Scholar 

  30. Rietbrock, N., Kuhlmann, J.: Clinical significance of distribution and elimination of cardiac glycosides. Internal symposion on clinical pharmacokinetics, (ed. W.A. Ritschel). Salzgitter-Ringelheim: 1975 (in preparation)

  31. Ruiz-Torres, A., Burmeister, H.: Stoffwechsel und Kinetik von β-Acetyldigoxin. Klin. Wschr.50 191–195 (1972)

    Google Scholar 

  32. Schaumann, W., Wegerle, R.: β-Methyldigoxin. I. Cardiotoxicität bei enteraler und parenteraler Gabe. Arzneimittel-Forsch.21 225–231 (1971)

    Google Scholar 

  33. Schaumann, W., Koch, K.: β-Methyl-digoxin. VII. Tissue distribution, positive inotropic and central action in cats in comparison with other digitalis glycosides. Naunyn-Schmiedeberg's Arch. Pharmacol.286 195–210 (1974)

    Google Scholar 

  34. Shapiro, W., Narahara, K., Taubert, K.: Relationship of plasma digitoxin and digoxin to cardiac response following intravenous digitalization in man. Circulation42 1065–1072 (1970)

    Google Scholar 

  35. Smith, Th.W., Butler, V.P., Haber, E.: Determination of therapeutic and toxic digoxin concentrations by radioimmunoassay. New Engl. J. Med.281 1212–1216 (1969)

    Google Scholar 

  36. Storz, H.: Die quantitative Wirksamkeit des Herzglykosids β-Methyldigoxin. Med. Welt (Berl.)21 2066–2070 (1970)

    Google Scholar 

  37. Weissler, A.M., Lewis, R.P., Leighton, R.F., Bush, Ch.A.: Comparative responses to the digitalis glycosides in man. Basic and clinical pharmacology of digitalis (eds. B.H. Marks, A.M. Weissler), p. 260. Springfield, Ill.: C.C. Thomas 1972

    Google Scholar 

  38. Zilly, W., Richter, E., Rietbrock, N.: Pharmacokinetics and metabolism of digoxin- and β-methyldigoxin-12α-3H in patients with acute hepatitis. Clin. Pharmacol. Ther.17 302–309 (1975)

    Google Scholar 

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Authors and Affiliations

  1. Dept. of Clinical Pharmacology, Klinikum Steglitz der Freien Universität Berlin, Berlin, Federal Republic of Germany

    N. Rietbrock, J. Guggenmos, J. Kuhlmann & U. Hess

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  1. N. Rietbrock
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  2. J. Guggenmos
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  3. J. Kuhlmann
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  4. U. Hess
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Rietbrock, N., Guggenmos, J., Kuhlmann, J. et al. Bioavailability and pharmacokinetics of β- methyldigoxin after multiple oral and intravenous doses. Eur J Clin Pharmacol 9, 373–379 (1976). https://doi.org/10.1007/BF00606551

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  • DOI: https://doi.org/10.1007/BF00606551

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