Skip to main content
SpringerLink
Log in

Pharmacokinetics of Digoxin and Derivatives

  • Chapter
Cardiac Glycosides

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 56 / 2))

Abstract

In the absence of sensitive analytical methods, estimation of the quantity of glycoside in the myocardium was at one time possible only by observing the pharmacologic effect in the intact animal, or in a heart—lung preparation, or in the embryonic chick heart (Weese, 1928, 1929; Lendle, 1935; Rothlin, 1944; Friedman and Bine, 1947; Bine et al., 1951; Rothlin and Bircher, 1954). Later, the direct detection of digitalis glycosides in various organs and tissues of the rat was achieved using the xanthydrol or m-dinitrobenzol reaction (Repke, 1958). Fluorescence techniques enabled additional inferences on the structure of the steroid nucleus to be obtained (Jensen, 1953; Wells et al., 1961; Jelliffe, 1967). The main disadvantage of the foregoing methods is the relatively low sensitivity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Agren, G., Ponten, J., Ronquist, G., Westermark, B.: Demonstration of an ATPase at the cell surface of intact normal and neoplasic human cells in culture. J. Cell. Physiol. 78, 171–176 (1971)

    PubMed  CAS  Google Scholar 

  • Allonen, H., Andersson, K.-E., Iisalo, E., Kanto, J., Stomblad, L.-G., Wettrell, G.: Passage of digoxin into cerebrospinal fluid in man. Acta Pharmacol. Toxicol. (Kbh.) 41, 193–201 (1977)

    CAS  Google Scholar 

  • Andersson, K.-E., Bertler, A., Wettrell, G.: Post-mortem distribution and tissue concentrations of digoxin in infants and adults. Acta Paediatr. Scand. 64, 497–504 (1975)

    CAS  Google Scholar 

  • Aronson, J.K.: Monitoring digoxin therapy: III Hdw useful are the nomograms ? Brit. J. Clin. Pharmacol. 5, 55–64 (1978)

    CAS  Google Scholar 

  • Bayliss, E.M., Hall, M.S., Lewis, G., Marks, V.: Effects of renal function on plasma digoxin levels in elderly ambulant patients in domiciliary practice. Br. Med. J. 1972 1, 338–341

    Google Scholar 

  • Bacz’ynski, R., Kokot, F.: Der EinfluĂŸ von Furosemid auf die Beta-methyl-Digoxin-Aus-scheidung im Urin. Dtsch. Med. Wochenschr. 103, 662–664 (1978)

    Google Scholar 

  • Bättig, P., Brune, K., Schmitt, H., Walz, D.: A pharmacokinetic slide-rule for more accurate drug treatment. Eur. J. Clin. Pharmacol. 7, 233–239 (1974)

    PubMed  Google Scholar 

  • Beermann, B.: The gastrointestinal uptake of methyldigoxin 12a-3H in man. Eur. J. Clin. Pharmacol. 5, 28–33 (1972)

    CAS  Google Scholar 

  • Beermann, B., Hellström, K., Rosen, A.: The absorption of orally administered 12a-3H digoxin in man. Clin. Sci. 43, 507–518 (1972)

    PubMed  CAS  Google Scholar 

  • Beller, G.A., Smith, T.W., Hood, W.B., jr.: Altered distribution of tritiated digoxin in the infarcted canine left ventricle. Circulation 46, 572–579 (1972)

    PubMed  CAS  Google Scholar 

  • Benthe, H.F.: Organverteilung verschiedener Herzglykoside. In: Digitalistherapie. Jahrmärker, H. (ed.), pp. 19–34. Berlin, Heidelberg, New York: Springer 1975

    Google Scholar 

  • Bine, R., Friedman, M., Byers, S.O., Bland, C.: The deposition of digitoxin in the tissues of the rat after parenteral injection. Circulation 4, 105–107 (1951)

    PubMed  CAS  Google Scholar 

  • Binnion, P.F., Morgan, L.M., Stevenson, H.M., Fletcher, E.: Plasma and myocardial digoxin concentrations in patients on the oral therapy. Brit. Heart J. 31, 636–640 (1969)

    PubMed  CAS  Google Scholar 

  • Bischoff, K.O., Flohr, E., Graben, N., Hager, W., Merguet, P.: Zur Therapie der experimentellen, chronischen Digitalisintoxikation durch Hämoperfusion. Z. Kardiol. 66, 656–662 (1977)

    PubMed  CAS  Google Scholar 

  • Bissett, J.K., Doherty, J.E., Flanigan, W.J., Dalrymple, G.V.: Tritiated digoxin. XIX Turnover studies in diabetes insipidus. Am. J. Cardiol. 31, 327–330 (1973)

    PubMed  CAS  Google Scholar 

  • Bloom, P.M., Nelp, W.B.: Relationships of the excretion of tritiated digoxin to renal function. Am. J. Med. Sci. 251, 133–136 (1966)

    PubMed  CAS  Google Scholar 

  • Bochner, F., Huffman, D.H., Shen, D.D., Azarnoff, D.L.: Bioavailability of digoxin-hydro-quinone complex: A new oral digoxin formulation. J. Pharm. Sci. 66, 644–647 (1977)

    PubMed  CAS  Google Scholar 

  • Bodem, G., Boldt, U., Ochs, H.: Konzentrationen von Digoxin und Beta-Methyldigoxin in Liquor und Plasma. Klin. Wochenschr. 55, 355–356 (1977)

    PubMed  CAS  Google Scholar 

  • Bonelli, J., Hruby, K., Magometschnigg, D., Hitzenberger, G., Kaik, G.: The bioavailability of beta-acetyldigoxin (Novodigal) alone and combined with osyfedrine (Ildamen-Novodigal). Int. J. Clin. Pharmacol. 15, 288–293 (1977)

    CAS  Google Scholar 

  • Brown, D.D., Dormois, J.C., Abraham, G.N., Lewis, K., Dixon, K.: Effect of furosemide on the renal excretion of digoxin. Clin. Pharmacol. Ther. 20, 395–400 (1976)

    PubMed  CAS  Google Scholar 

  • Caldwell, J.H., Cline, Ch.R.: Biliary excretion of digoxin in man. Clin. Pharmacol. Ther. 19, 410–415 (1976)

    PubMed  CAS  Google Scholar 

  • Caroll, P.R., Gelbart, A., O’Rourke, M.F., Shortus, J.: Digoxin concentrations in the serum and myocardium of digitalised patients. Aust. N. Z. J. Med. 3, 400–403 (1973)

    Google Scholar 

  • Carruthers, S.G., Cleland, J., Kelley, J.G., Lyous, S.M., McDevitt, D.G.: Plasma and tissue digoxin concentrations in patients undergoing cardiopulmonary bypass. Brit. Heart J. 37, 313–320 (1975)

    PubMed  CAS  Google Scholar 

  • Chamberlain, D.A.: The ratio between myocardial and plasma levels of digoxin. In: Digitalis. Storstein, O. (ed.), p. 262. Oslo: Gyldendal, Norsk Forlag 1973

    Google Scholar 

  • Clark, D.R., Kalman, S.M.: Dihydrodigoxin: A common metabolite of digoxin in man. Drug Metab. Disp. 2, 148–150 (1974)

    CAS  Google Scholar 

  • Coltart, D.J., Billingham, M., Stinson, B.E., GĂ¼llner, H.G., Goldman, R.H., Kalman, S.M., Harrison, D.C.: Distribution of digoxin in the human heart. Postgrad. Med. J. 51, 330–333 (1975)

    PubMed  CAS  Google Scholar 

  • Coltart, D.J., GĂ¼llner, H.G., Billingham, M., Goldman, R.H., Stinson, E.B., Kalman, S.M., Harrison, D.C.: Physiological distribution of digoxin in human heart. Brit. Med. J. 1974 4, 733–736

    PubMed  CAS  Google Scholar 

  • Coltart, D.J., Howard, M., Chamberlain, D.: Myocardial and skeletal muscle concentrations of digoxin in patients on longterm therapy. Brit. Med. J. 1972 1, 318–319

    Google Scholar 

  • Danon, A., Horowitz, J., Ben-Zvi, Z., Kaplanski, J., Glick, S.: An outbreak of digoxin intoxication. Clin. Pharmacol. Ther. 21, 643–646 (1977)

    PubMed  CAS  Google Scholar 

  • Dengler, H.J., Bodem, G., Wirth, K.: Pharmakokinetische Untersuchungen mit H3-digoxin and H3-Lanatosid beim Menschen. Arzneim. Forsch. 23, 64–74 (1973)

    CAS  Google Scholar 

  • Dettli, L., Ohnhaus, E.E., Spring, P.: Digoxin dosage in patients with impaired kidney function. Brit. J. Pharmacol. 44, 373P (1972)

    CAS  Google Scholar 

  • Dobbs, S.M., Mawer, G.E., Rodgers, E.M., Woodcock, B.G., Lucas, S.B.: Can maintenance digoxin dose requirements be predicted ? Brit. J. Clin. Pharmacol. 3, 231–237 (1976)

    CAS  Google Scholar 

  • Doering, W.: Quinidine-digoxin interaction: Pharmacokinetics, underlying mechanism and clinical implication. N. Engl. J. Med. 301, 400–404 (1979)

    PubMed  CAS  Google Scholar 

  • Doherty, J.E., Ferrill, C.B., Trowbin, E.J.: Localisation of the renal excretion of the tritiated digoxin. Am. J. Med. Sci. 258, 181–189 (1969)

    PubMed  CAS  Google Scholar 

  • Doherty, J.E., Flanigan, W.J., Murphy, M.L., Bulloch, R.J., Dalrymple, J.W., Beard, O.W., Perkins, W.H.: Tritiated digoxin. Enterohepatic circulation and excretion studies in human volunteers. Circulation 42, 867–873 (1970)

    PubMed  CAS  Google Scholar 

  • Doherty, J.E., Flanigan, W.J., Perkins, W.H.: Tritiated digoxin excretion of patients following renal transplantation. Circulation 38, 865–869 (1968)

    Google Scholar 

  • Doherty, J.E., Flanigan, W.J., Perkins, W.H., Ackerman, G.L.: Studies with tritiated digoxin in anephric human subjects. Circulation 35, 298–303 (1967)

    PubMed  CAS  Google Scholar 

  • Doherty, J.E., Kane, J.J.: Clinical pharmacology of digitalis glycosides. Ann. Rev. Med. 26, 159–171 (1975)

    PubMed  CAS  Google Scholar 

  • Doherty, J.E., Perkins, W.H.: Studies with tritiated digoxin in human subjects after intravenous administration. Am. Heart J. 63, 528–536 (1962)

    PubMed  CAS  Google Scholar 

  • Eckstein, M., KĂ¼hne, T.: Kinetik and Stoffwechsel von α-and ĂŸ-acetyldigoxin im menschlichen Organismus. Dissertation. Faculty of Medicine. Free University Berlin 1976

    Google Scholar 

  • Fischer, H.: Ăœber Aufnahme, Bindung and Abbau von Digitalisstoffen and die sich daraus ergebenden Beziehungen zur Wirkung am Herzen. Naunyn Schmiedebergs Arch. Exp. Path. Pharmak. 130, 11–193 (1928)

    Google Scholar 

  • Flasch, H.: Die biologische VerfĂ¼gbarkeit von ĂŸ-acetyldigoxin and digoxin. Klin. Wochenschr. 53, 873–877 (1975)

    PubMed  CAS  Google Scholar 

  • Flasch, H., Heinz, N.: Konzentration von Herzglykosiden im Myokard and im Gehirn. Arzneim. Forsch. 26, 1213–1216 (1976)

    CAS  Google Scholar 

  • Friedman, M., Bine, R.: Employment of the embryonic duck heart for the detection of minute amounts of a digitalis glycoside (Lanatoside C). Proc. Soc. Exp. Biol. Med. 64, 162–765 (1947)

    PubMed  CAS  Google Scholar 

  • Friedmann, M., St. George, S., Bine, R., Byers, S.O., Bland, C.: The renal excretion of digitoxin in the acute and chronic cardiac patient. Circulation 6, 367–370 (1952)

    Google Scholar 

  • Gault, H.M., Jeffrey, J.R., Chirito, E., Ward, L.L.: Studies of digoxin dosage, kinetics, and serum concentrations in renal failure and review of literature. Nephron 17, 161–187 (1976)

    PubMed  CAS  Google Scholar 

  • Gault, M.H., Sugden, D., Maloney, C., Ahmed, M., Tweeddale, M.: Biotransformation and elimination of digoxin with normal and minimal renal function. Clin. Pharmacol. Ther. 25, 499–513 (1979)

    PubMed  CAS  Google Scholar 

  • Gayes, J.M., Greenblatt, D.J., Lloyd, B.L., Harmatz, J.S., Smith, T.W.: Cerebrospinal fluid digoxin concentrations in humans. J. Clin. Pharmac. 18, 16–20 (1978)

    CAS  Google Scholar 

  • Gilfrich, H.J., Okonek, S., Manns, M., Schuster, C.J.: Digoxin and digitoxin elimination in man by charcoal hemoperfusion. Klin. Wochenschr. 56, 1179–1183 (1978)

    PubMed  CAS  Google Scholar 

  • Gorodischer, R., Jusko, W J, Sumner, J.Y.: Tissue and erythrocyte distribution of digoxin in infants. Clin. Pharmacol. Ther. 19, 256–263 (1976)

    PubMed  CAS  Google Scholar 

  • Greeff, K., Hafner, D., Strobach, H., Wirth, K.E.: Vergleich der BioverfĂ¼gbarkeit bzw. enteralen Resorption des Digoxins, ĂŸ-Acetyldigoxins und ĂŸ-Methyldigoxins. Arzneim. Forsch. 27, 2358–2364 (1977)

    CAS  Google Scholar 

  • Greenblatt, D.J., Duhme, D.W., Koch-Weser, J., Smith, Th.W.: Evaluation of digoxin Bio-availability in single-dose studies. N. Engl. J. Med. 289, 651–654 (1973)

    PubMed  CAS  Google Scholar 

  • Greenblatt, D.J., Duhme, D.W., Koch-Weser, J., Smith, Th.W.: Bioavailability of digoxin tablets and elixir in the fasting and post-prandial states. Clin. Pharmacol. Ther. 16, 444–448 (1974)

    PubMed  CAS  Google Scholar 

  • Greenblatt, D.J., Smith, T.W., Koch-Weser, J.: Bioavailability of drugs: The digoxin dilemma. Clin. Pharmacokinet. 1, 36–51 (1976)

    PubMed  CAS  Google Scholar 

  • GĂ¼llner, H.-G., Stinson, E.B., Harrison, D.C., Kalman, S.M.: Correlation of serum concentrations with heart concentrations of digoxin in human subjects. Circulation 50, 653–655 (1974)

    PubMed  Google Scholar 

  • Haack, E., Kaiser, F., Spingler, F., Spingler, H.: Digoxingenin-mono-und bis-digitoxosid, zwei neue Glykoside der Digitalis lanata. Naturwissenschaften 44, 633–634 (1957)

    CAS  Google Scholar 

  • Haasis, R., Larbig, D.: Radioimmunologische Bestimmungen der Glykosidkonzentrationen im menschlichen Gehirngewebe. Verh. Dtsch. Ges. Kreislaufforsch. 42, 275–277 (1976)

    PubMed  CAS  Google Scholar 

  • Haasis, R., Larbig, D., Stunkat, R., Bader, H., Seboldt, H.: Radioimmunologische Bestimmung der Glykosidkonzentration im menschlichen Gewebe. Klin. Wochenschr. 55, 23–30 (1977)

    PubMed  CAS  Google Scholar 

  • Hager, D., Fenster, P., Mayersohn, M., Perrier, D., Graves, P., Marcus, F.I., Goldman, S.: Digoxin-quinidine interaction pharmacokinetic evaluation. N. Engl. J. Med. 300, 1238–1241 (1979)

    PubMed  CAS  Google Scholar 

  • Härtel, G., Kyllönen, K., Merikallio, E., Ojala, K., Manninen, V., Reissel, P.: Human serum and myocardium digoxin. Clin. Pharmacol. Ther. 19, 153–157 (1976)

    PubMed  Google Scholar 

  • Halkin, H., Sheiner, L.B., Peck, C.C., Melmon, K.L.: Determinants of the renal clearance of digoxin. Clin. Pharmacol. Ther. 17, 385–394 (1975)

    PubMed  CAS  Google Scholar 

  • Herrmann, I., Repke, K.: Ăœber die Biotransformation von Digitoxin und Digitoxigenin in der menschlichen Leber. Monatsber. Dtsch. Akad. Wissenschaften Berlin 5, 140–143 (1963a)

    CAS  Google Scholar 

  • Herrmann, J., Repke, K.: Ăœber das Glucuronsäurekonjugat eines Cardenolidgenins (3Epidigitoxigenin). Experientia (Basel) 19, 472–474 (1963b)

    CAS  Google Scholar 

  • Herrmann, I., Repke, K.: Transformations of cardenolids by microorganism of the intestine. Abh. dtsch. Akad. Wissenschaften Berlin. S. 115–119 (1968)

    Google Scholar 

  • Hinderling, P. H., Garret, E.R., Wester, R.C.: Pharmacokinetics of β-methyldigoxin in healthy humans I Intravenous studies. J. Pharm. Sci. 66, 242–253 (1977)

    PubMed  CAS  Google Scholar 

  • Hopkins, B.E., Taylor, R.R.: Digoxin distribution in the dog’s left ventricle in the presence of coronary artery ligation. J. molec. cell. Cardiol. 5, 197–203 (1973)

    CAS  Google Scholar 

  • Huffman, D.H., Azarnoff, D.L.: Absorption of orally given diguxin preparations. J. Amer. Med. Ass. 222, 957–960 (1972)

    CAS  Google Scholar 

  • Iisalo, E.: Clinical pharmacokinetics of digoxin. Clin. Pharmacokinet. 2, 1–16 (1977)

    PubMed  CAS  Google Scholar 

  • Iisalo, E., Forsstrom, J.: Elimination of digoxin during maintenance hemodialysis. Ann. clin. Res. 6, 203–206 (1974)

    PubMed  CAS  Google Scholar 

  • Jelliffe, R.W.: An ultramicro fluorescent spray reagent for detection and quantification of cardiotonic steroids on thin-layer chromatograms. J. Chromatog. 27, 172–179 (1967)

    CAS  Google Scholar 

  • Jensen, K.B.: Fluorometric determination of digitoxigenin. Acta Pharmacol. Toxicol. 9, 66–74 (1953)

    CAS  Google Scholar 

  • Jusko, W.J., Weintraub, M.: Myocardial distribution of digoxin and renal function. Clin. Pharmacol. Ther. 16, 449–454 (1974)

    PubMed  CAS  Google Scholar 

  • Kaiser, F., Haack, E., Spingler, H.: Ober die Mono-und Bisdigitoxoside des Digitoxigenins, Gitoxigenins und Gitaloxigenins. Justus Liebig Ann. Chem. 603, 75–88 (1957)

    CAS  Google Scholar 

  • Karjalainen, J., Ojala, K., Reissell, P.: Tissue concentrations of digoxin in autopsy material. Acta Pharmacol. Toxicol. 34, 385–390 (1974)

    CAS  Google Scholar 

  • Keller, F., Rietbrock, N.: Bioavailability of digoxin: Some pitfalls and problems. Int. J. Clin. Pharmacol. 15, 549–556 (1977)

    CAS  Google Scholar 

  • Kelsey, F.E.: Radioactive digitoxin. Illinois Med. J. 100, 309–310 (1951)

    CAS  Google Scholar 

  • Kim, P.W., Krasula, R.W., Soyka, L.F., Hastreiter, A.R.: Postmortem tissue digoxin concentrations in infants and children. Circulation 52, 1128–1131 (1975)

    PubMed  CAS  Google Scholar 

  • Klotz, U., Antonin, K.H., Bieck, P.R.: Bioavailability of ĂŸ-acetyldigoxin after single and repeated doses of tablets and solutions. Eur. J. Clin. Pharmacol. 10, 417–424 (1976)

    PubMed  CAS  Google Scholar 

  • Kongola, G.W.M., Mawer, G.E., Woodcock, B.G.: Steady-state pharmacokinetics of /3methyldigoxin and digoxin. Br. J. Clin. Pharmacol. 3, 954P - 955P (1976)

    CAS  Google Scholar 

  • Koup, J.R., Greenblatt, D.J., Jusko, W.J., Smith, T.W., Koch-Weser, J.: Pharmacokinetics of digoxin in normal subjects after intravenous bolus and infusion doses. J. Pharmacokinet. Biopharmaceut. 3, 181–192 (1975)

    CAS  Google Scholar 

  • Koup, J., Jusko, W.T., Elwood, C.M., Kohli, R.K.: Digoxin pharmacokinetics: Role of renal failure in dosage regimen design. Clin. Pharmacol. Ther. 18, 9–21 (1976)

    Google Scholar 

  • Kramer, P.: Digitalis pharmacokinetics and therapy with respect to impaired renal function. Klin. Wochenschr. 55, 1–11 (1977)

    PubMed  Google Scholar 

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

    CAS  Google Scholar 

  • Kramer, P., Matthias, C., Matthaei, D., Scheler, F.: Elimination von Herzglykosiden durch Hämofiltration. Verh. Dtsch. Ges. Inn. Med. 83, 1618–1621 (1977)

    PubMed  CAS  Google Scholar 

  • Kramer, P., Quellhorst, E., Horenkamp, J., Scheler, F.: Dialysance and prozentuale Elimination verschiedener Herzglykoside während der Hämo-und Peritonealdialyse. Klin. Wochenschr. 50, 609–613 (1972)

    PubMed  CAS  Google Scholar 

  • Kramer, P., Scheler, F.: Renale Eliminationskinetik verschiedener Herzglykoside. Dtsch. Med. Wochenschr. 97, 1485–1490 (1972)

    PubMed  CAS  Google Scholar 

  • Kuhlmann, J.: Verteilung von Herzglykosiden im Organismus. Klinisch-pharmakologische Grundlagen der Therapie. Habilitationsschrift, Freie Universität Berlin 1978

    Google Scholar 

  • Kuhlmann, J., Abshagen, U., Rietbrock, N.: Pharmacokinetics and metabolism of digoxigenin-monodigitoxoside in man. Eur. J. Clin. Pharmacol. 7, 87–94 (1974)

    CAS  Google Scholar 

  • Kuhlmann, J., Kötter, E., Leitner, G. von, Arbeiter, G., Schröder, R., Rietbrock, N.: Concentration of digoxin, methyldigoxin, digitoxin, and ouabain in the myocardium of the dog following coronary occlusion. Naunyn Schmiedebergs Arch. Pharmacol. 287, 399–411 (1975)

    PubMed  CAS  Google Scholar 

  • Kuhlmann, J., Rietbrock, N., Schnieders, B.: Tissue distribution and elimination of digoxin and methyldigoxin after single and multiple doses in dogs. J. Cardiovasc. Pharmacol. 1, 219–234 (1979)

    PubMed  CAS  Google Scholar 

  • Kuschinsky, K., Ullmann, H., Zwieten, P.A. van: A comparison of the accumulation and release of H3-ouabain and H3-digitoxin by guinea-pig heart muscle. Br. J. Pharmacol. Chemother. 32, 598–608 (1968)

    PubMed  CAS  Google Scholar 

  • Larbig, D., Kochsiek, K.: Zur radioimmunochemischen Bestimmung von Digoxin und Digoxinderivaten. Dtsch. Med. Wochenschr. 97, 1310–1312 (1972)

    PubMed  CAS  Google Scholar 

  • Laws, E.R., O’Connor, J.S.: ATPase in human brain tumors. J. Neurosurg. 33, 167–171 (1970)

    PubMed  CAS  Google Scholar 

  • Lendle, L.: Digitaliskörper und verwandte herzwirksame Glykoside (Digitaloide). In: Heffter-Heubners Handbuch der experimentellen Pharmakologie, Ergänzungswerk, Bd.1, S. 11. Berlin: Springer 1935

    Google Scholar 

  • Lindenbaum, J.: Bioavailability of digoxin tablets. Pharmacol. Rev. 25, 229–237 (1973)

    PubMed  CAS  Google Scholar 

  • Luccini, C.R., Padeletti, L., Masilii, A., Porciani, M.C., Bertini, G.: Digoxin clearance and glomerular filtration rate. Int. J. Pharmacol. Biopharm. 17, 186–188 (1979)

    Google Scholar 

  • Luchi, R.J., Gruber, J.W.: Unusually large digitalis requirements study of altered digoxin metabolism. Am. J. Med. 45, 322–328 (1968)

    PubMed  CAS  Google Scholar 

  • Malcolm, A.D., Leung, F.Y., Fuchs, J.C.A., Duarte, J.E.: Digoxin kinetics during furosemide administration. Clin. Pharmacol. Ther. 21, 567–574 (1977)

    PubMed  CAS  Google Scholar 

  • Marcus, F.I., Burkhalter, L., Cuccia, C., Pavlovich, J., Kapadia, G.G.: Administration of tritiated digoxin with and without a loading dose. A metabolic study. Circulation 24, 865–874 (1966a)

    Google Scholar 

  • Marcus, F.I., Dickerson, J., Pippin, S., Stafford, M., Bressler, R.: Digoxin bioavailability: Formulations and rates of infusions. Clin. Pharmacol. Ther. 20, 253–259 (1976)

    PubMed  CAS  Google Scholar 

  • Marcus, F.I., Nimmo, L., Kapadia, G.G., Goldsmith, C.: The effect of acute hypokalemia on the myocardial concentration and body distribution of tritiated digoxin in the dog. J. Pharmacol. Exp. Ther. 178, 271–280 (1971)

    PubMed  CAS  Google Scholar 

  • Marcus, F.I., Peterson, A., Salel, A., Scully, J., Kapadia, G.G.: The metabolism of tritiated digoxin in renal insufficiency in dogs and man. J. Pharmacol. Exp. Ther. 152, 372–382 (1966b)

    PubMed  CAS  Google Scholar 

  • Mawer, G.: Cardiac glycosides in atrial fibrillation. In: Methods in clinical pharmacology. Rietbrock, N., Woodcock, B.G., Neuhaus, G. (eds.), pp. 106–113. Braunschweig: Vie-weg 1980

    Google Scholar 

  • Nyberg, L., Bratt, L., Forsgren, A., Hugosson, S.: Bioavailability of digoxin from tablets I. In vitro characterization of digoxin tablets. Acta Pharm. Succica 11, 447–458 (1974)

    CAS  Google Scholar 

  • Okita, G.T., Talso, P.J., Curry, J.H., Smith, F.D., Geiling, E.M.K.: Metabolic fate of radio-active digitoxin in human subjects. J. Pharmacol. 115, 371–379 (1955)

    CAS  Google Scholar 

  • Ohnhaus, E.E., Masson, J.P.: The influence of therapeutic doses of spironolactone on the liver microsomal enzyme system and digoxin elimination in man. Br. J. Clin. Pharmacol. 4, 693P - 640P (1977)

    Google Scholar 

  • Peters, U., Falk, L.C., Kalman, S.M.: Digoxin metabolism in patients. Arch. Intern. Med. 138, 1074–1076 (1978)

    PubMed  CAS  Google Scholar 

  • Peters, U., Kalman, S.M.: Dihydrierte Metaboliten des Digoxins: Klinische Bedeutung und Nachweisverfahren. Z. Kardiol. 67, 342–345 (1978)

    PubMed  CAS  Google Scholar 

  • Petersen, R.H., Flasch, H., Heinz, N.: Darstellung und Eigenschaften einiger Glukuronide und Sulfate von Cardenoliden und Cardenolidglykosiden. Arzneim. Forsch. 27, 642–649 (1977)

    CAS  Google Scholar 

  • Pfleger, K., Kolassa, N., Heinrich, W., Schneider, M.: Pharmakokinetik und Wirkung von Digitoxin und Ouabain am isolierten Herzen von Meerschweinchen und Ratte. Arch. Int. Pharmacodyn. 216, 130–143 (1975)

    PubMed  CAS  Google Scholar 

  • Redfors, A., Bertler, A., Schuller, H.: The ratio between myocardial and plasma levels of digoxin in man. In: Digitalis. Storstein, O. (ed.), pp. 265–269. Oslo: Gyldendal Norsk Forlag 1973

    Google Scholar 

  • Repke, K.: Die chemische Bestimmung von Digitoxin in Geweben und Ausscheidung. Arch. Exp. Path. Pharmakol. 233, 261–270 (1958)

    CAS  Google Scholar 

  • Repke, K.: Ăœber Spaltung und Hydroxylierung von Digitoxin bei der Ratte. Naunyn Schmiedebergs Arch. Exp. Path. Pharmakol. 237, 34–48 (1959)

    CAS  Google Scholar 

  • Repke, K.: Biochemie und Klinik der Digitalis. Internist 7, 418–426 (1966)

    PubMed  CAS  Google Scholar 

  • Repke, K.: Stoffwechsel und Wirkung von Digitalisglykosiden. Ost. Apoth. Ztg. 24, 515 (1970)

    CAS  Google Scholar 

  • Repke, K.: Biochemische Aspekte der Digitalistherapie. Tagungsber. Ges. Inn. Med. DDR 26, 8–16 (1971)

    Google Scholar 

  • Repke, K.: Biochemische Grundlagen der Entwicklung neuartiger Herzmittel des Digitalistyps. Pharmazie 27, 693–701 (1972)

    PubMed  CAS  Google Scholar 

  • Reuning, R.H., Sams, R.A., Notari, R.E.: Role of pharmacokinetics in drug dosage adjustment. Pharmacologic effect kinetics and apparent volume of distribution of digoxin. J. Clin. Pharmacol. 4, 127–141 (1973)

    Google Scholar 

  • Rietbrock, N., Abshagen, U.: Stoffwechsel und Pharmakokinetik der Lanataglykoside beim Menschen. Dtsch. Med. Wochenschr. 98, 117–122 (1973)

    PubMed  CAS  Google Scholar 

  • Rietbrock, N., Abshagen, U., Bergmann, K. v., Rennekamp, H.: Disposition of ĂŸ-methyldigoxin in man. Eur. J. Clin. Pharmacol. 9, 105–114 (1975)

    CAS  Google Scholar 

  • Rietbrock, N., Guggenmos, J., Kuhlmann, J., Hess, U.: Bioavailability and pharmacokinetics of ĂŸ-methyldigoxin after multiple oral and intravenous doses. Eur. J. Clin. Pharmacol. 9, 373–379 (1976)

    CAS  Google Scholar 

  • Rietbrock, N., Kuhlmann, J.: Clinical significance of distribution and elimination of cardiac glycosides. In: Clinical pharmacokinetics. Proc. Internat. Symp. Ritschel, W.A. (ed.), pp. 57–65. Stuttgart, New York: Fischer 1977

    Google Scholar 

  • Rietbrock, N., Kuhlmann, J., Vöhringer, H.-F.: Pharmakokinetik von Herzglycosiden und klinische Konsequenzen. Fortschr. Med. 95, 909–954 (1977a)

    PubMed  CAS  Google Scholar 

  • Rietbrock, I., Streng, H., Pesold, R.: Glykosidplasma-Konzentrationen bei operativ und intensiv versorgten Patienten. Klin. Wochenschr. 56, 503–517 (1978)

    PubMed  CAS  Google Scholar 

  • Rietbrock, N., Vöhringer, H.-F.: Metabolism and excretion of 3H-digitoxin in the rat. Biochem. Pharmacol. 23, 2567–2575 (1974)

    PubMed  CAS  Google Scholar 

  • Rietbrock, N., Vöhringer, H.F., Kuhlmann, J.: Der Metabolismus herzwirksamer Glykoside. Herz/Kreisl. 9,825–832 (1977b)

    CAS  Google Scholar 

  • Rietbrock, N., Alken, R.G.: Color vision deficiencies: A common sign of mitoxication in chronically digoxin-treated patients. J. Cardiovasc. Pharmacol. 2, 93–99 (1980)

    PubMed  CAS  Google Scholar 

  • Risler, T., Arnold, G., Grabensee, B.: Ist die Hämoperfusion zur Behandlung der Digoxin-Intoxikation geeignet? Z. Kardiol. 68, 313–319 (1979)

    PubMed  CAS  Google Scholar 

  • Roman, R.J., Kauker, M.L.: Renal tubular transport of 3H-digoxin in saline diuresis in rats.: Evaluation by micropuncture. Circ. Res. 38, 185–191 (1976)

    PubMed  CAS  Google Scholar 

  • Rothlin, E.: Beitrag zum Problem der Verteilung der Pharmaka im Organismus, im besonderen herzwirksame Glykoside. Schweiz. Med. Wochenschr. 8, 217–220 (1944)

    Google Scholar 

  • Rothlin, E., Bircher, R.: Pharmacodynamische Grundlagen der Therapie mit herzwirksamen Glykosiden. Ergeb. Inn. Med. Kinderheilk. 5, 457–552 (1954)

    CAS  Google Scholar 

  • Rotmensch, H.H., Graff, E., Terdiman, R., Aviram, A., Ayzenberg, O., Laniado, S.: Furosemide-induced forced diuresis in digoxin intoxication. Arch. Intern. Med. 138, 1495–1497 (1978)

    PubMed  CAS  Google Scholar 

  • Sanchez, N., Sheiner, L.B., Halkin, H., Melmon, K.L.: Pharmacokinetics of digoxin: Interpreting bioavailability. Br. Med. J. 1973 4, 132–134

    PubMed  CAS  Google Scholar 

  • Schmoldt, A., Benthe, H.F., Haberland, G.: Digitoxin metabolism by rat liver microsomes. Biochem. Pharmacol. 24, 1639–1641 (1975)

    PubMed  CAS  Google Scholar 

  • Schott, G.D., Holt, D.W., Hayler, A.A.M.: Penetration of digoxin into cerebrospinal fluid. Postgrad. Med. J. 52 (613), 700–702 (1976)

    PubMed  CAS  Google Scholar 

  • Schwabe, L., Rietbrock, N., Frömming, K.H.: Der EinfluĂŸ von Ă„thanol auf die in vitro und in vivo Freisetzung von Digoxin aus Tablettenpräparaten. Pharm. Ind. 41, 1207–1212 (1979)

    CAS  Google Scholar 

  • Sheiner, L.B., Rosenberg, B., Melmon, K.L.: Modeling of individual pharmacokinetics for computer aided drug usage. Comput. Biomed. Res. 5, 441–459 (1972)

    Google Scholar 

  • Siersbaek-Nielsen, K., Melholm Hansen, J., Kampmann, J., Kristensen, M.: Rapid evaluation of creatinine clearance. Lancet 1971 1, 1133–1134

    PubMed  CAS  Google Scholar 

  • Somogyi, G., KĂ¢ldor, A., Jankovics, A.: A liquor cerebrospinĂ¢lis digitalis szintjĂ©nek vizsgalata. Adatok a digitalis glykozidĂ¢k idegrendszeri hatĂ¢sĂ¢nak tanulmĂ¢nyozĂ¢sĂ¢hoz. Orv. Hetil. 113, 804–805 (1972)

    PubMed  CAS  Google Scholar 

  • Steiness, E.: Renal tubular secretion of digoxin. Circulation 50, 103–107 (1974)

    PubMed  CAS  Google Scholar 

  • Steiness, E.: Suppression of renal excretion of digoxin in hypokalemic patients. Clin. Pharmacol. Ther. 23, 511–514 (1978)

    PubMed  CAS  Google Scholar 

  • Sumner, D.J., Russell, A.J.: Digoxin pharmacokinetics: Multicompartmental analysis and its clinical implications. Brit. J. Clin. Pharmacol. 3, 221–229 (1976)

    CAS  Google Scholar 

  • Thompson, A.J., Hargis, J., Murphy, M.L., Doherty, J.E.: Experimental myocardial infarction (MI), serum levels and tissue concentration of H3-digoxin. Clin. Res. 20, 401 (1972)

    Google Scholar 

  • Tilstone, W.J., Semple, P.F., Lawson, D.H., Boyle, J.A.: Effects of furosemide on glomerular filtration rate and clearance of practolol, digoxin, cephaloridin, and gentamicin. Clin. Pharmacol. Ther. 22, 389–394 (1977)

    PubMed  CAS  Google Scholar 

  • Tozer, T.N.: Nomogram for modification of dosage regimens in patients with chronic renal function impairment. J. Pharmacokinet. Biopharmaceut. 2, 13–28 (1974)

    Google Scholar 

  • Tsutsumi, E., Fujiki, H., Takeda, H., Fukushima, H.: Effect of furosemide on serum clearance and renal excretion of digoxin. J. Clin. Pharmacol. 19, 200–204 (1979)

    PubMed  CAS  Google Scholar 

  • Van der Vijgh, W.J.: Pharmacokinetic aspects of digoxin in patients with terminal renal failure. II. On hemodialysis. Int. J. Clin. Pharmacol. Biopharm. 15, 255–259 (1977)

    PubMed  Google Scholar 

  • Vöhringer, H.-F.: Pharmakokinetik von Digitoxin, Digitoxigenin-monodigitoxosid und Digitoxigenen-didesoxyrhamnosid beim Menschen unter besonderer BerĂ¼cksichtigung niereninsuffizienter Patienten. Habilitationsschrift, Freie Universität Berlin 1978

    Google Scholar 

  • Waldorf, S., Andersen, J.D., Heeboll-Nielsen, N., Nielsen, O.G., Moltke, E., Sorensen, U., Steiness, E.: Spironolactone-induced changes in digoxin kinetics. Clin. Pharmacol. Ther. 24, 162–167 (1978)

    Google Scholar 

  • Watson, E., Clark, D.R., Kalman, S.M.: Identification by gas chromatography-mass spectroscopy of dihydrodigoxin: A metabolite of digoxin in man. J. Pharmacol. Exp. Ther. 184, 424–431 (1973)

    PubMed  CAS  Google Scholar 

  • Weese, H.: Digitalisverbrauch und Digitaliswirkung im WarmblĂ¼ter. I. Mitt. Die Effektivdosen verschiedener Digitalisglykoside fĂ¼r das Herz. Naunyn Schmiedebergs Arch. Exp. Path. Pharmakol. 135, 228–244 (1928)

    CAS  Google Scholar 

  • Weese, H.: Digitalisverbrauch und Digitaliswirkung im WarmblĂ¼ter. II. Mitt. Der extracardiale Digitalisverbrauch und die Bedingungen der Glykosidbindung am Herzen. Naunyn Schmiedebergs Arch. Exp. Path. Pharmak. 141, 329–350 (1929)

    CAS  Google Scholar 

  • Weiner, I.M.: Renal physiology. In: Handbook of Physiology. Orloff, R., Berliner, R.W. (eds.), pp. 521–554. Washington D. C.: Amer. Physiol. Soc. 1973

    Google Scholar 

  • Weinmann, J., Hasford, J., Kuhlmann, J., Bippus, P.H., Lichey, J., Rietbrock, N.: Digoxinkonzentrationen in Plasma und Gewebe. Med. Klin. 74, 613–619 (1979)

    PubMed  CAS  Google Scholar 

  • Wells, D., Katzung, B., Meyers, F.H.: Spectrofluorometric analysis of cardiotonic steroids. J. Pharm. Pharmacol. 13, 389–395 (1961)

    PubMed  CAS  Google Scholar 

  • Wettrell, G., Anderson, K.-E., Bertter, A., Lundstrom, N.R.: Concentration of digoxin in plasma and urine in neonates, infants, and children with heart disease. Acta Paediat. Scand. 63, 705–710 (1974)

    PubMed  CAS  Google Scholar 

  • Williams, R., Flanigan, St., Bissett, J., Doherty, J.: Differential uptake of tritiated digoxin in benign and malignant central nervous system neoplasms. Am. J. Med. Sci. 272, 132–137 (1976)

    PubMed  CAS  Google Scholar 

  • Yatzidis, H., Voudiclari, S., Oreopoulos, D., Tsaparas, N., Triantaphyllids, D., Gavras, C., Stavroulaki, A.: Treatment of severe barbiturate poisoning. Lancet 1965 2, 216–217

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. N. Rietbrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. G. Woodcock
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Instituts fĂ¼r Pharmakologie, Universität DĂ¼sseldorf, MoorenstraĂŸe 5, D-4000, DĂ¼sseldorf, Deutschland

    Kurt Greeff (Direktor) (Direktor)

Rights and permissions

Reprints and permissions

Copyright information

© 1981 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Rietbrock, N., Woodcock, B.G. (1981). Pharmacokinetics of Digoxin and Derivatives. In: Greeff, K. (eds) Cardiac Glycosides. Handbook of Experimental Pharmacology, vol 56 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-68166-0_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-68166-0_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-68168-4

  • Online ISBN: 978-3-642-68166-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation