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Resorption, Verteilung und Galle-Ausscheidung einiger 3H-markierter Derivate des Helveticosols

  • F. Zielske
  • W. Voigtländer
  • W. Schaumann
Chapter

Schlüsselwörter

Herzglykosid Radioaktive Markierung Pharmakokinetik Arzneimittelmetabolismus Resorption 

Summary

Absorption, Tissue Distribution and Biliary Excretion of some 3H-labelled Derivatives of Helveticosol.

Helveticosol (strophanthidol-monodigitoxoside) and some of its esters and ethers were labelled with tritium by reduction of the C19-aldehyde group of helveticoside and the corresponding derivatives. Investigations on absorption, distribution and excretion in anaesthetized guinea-pigs gave the following results:
  1. 1

    Absorption was calculated from the percentage of the injected radioactivity which disappeared within two hours from an intestinal loop. With helveticosol as well as its mono- and dimethylether, there was a good agreement between this estunate of absorption and that derived from the relation of equiactive doses on intravenous and intraduodenal application. The absorption of diacetyl- and di-propionyl-helveticosol was less than expected from their activity on enterai application. This was explained by hydrolysis into more active metabolites.

     
  2. 2

    The distribution volume, calculated from the content of the body and the blood level, was lower after intraduodenal than after intravenous application. This was difficult to explain since there was no difference in the distribution coefficients of liver and heart and between the metabolites found in the blood after intravenous infusion or intraduodenal injection. There was no significant difference between the distribution volume after intraportal and intravenous infusion of monomethyl-helveticosol.

     
  3. 3

    Biliary excretion was measured after intravenous and intraduodenal administration and correlated with the mean blood and tissue levels. The glycosides which were best absorbed from the intestine were excreted most rapidly in the bile.

     

Key-Words

Cardioglycoside Labelled Compound Drug Metabolism Pharmacokinetics Absorption Gastrointestinal 

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Literatur

  1. Bray, G.A.: A simple efficient liquid scintillator for aqueous solutions in a liquid scintillation counter. Analyt. Biochem. 1, 279 (1960).CrossRefGoogle Scholar
  2. Dost, F.H., u. E. Gladtke: Ein Verfahren zur Ermittlung der Bilanz einverleibter Stoffe ohne Kenntnis der Ausscheidung. Z. klin. Chem. 1, 14 (1963).Google Scholar
  3. Fleishman, D.G., and V.V. Glazunow: An external standard as a means of determining the efficiency and background of a liquid scintillator. Pribory i Tekhn. Eksperim. 7, 55 (1962).Google Scholar
  4. Hayes, F.N., A.G. Schrodt, and J.A. Gibbs: Application of external standardization to automatic liquid scintillation counting, in Advances in Tracer Methodology, Ed. S. Rothschild, Vol. 3, Proc. 9th and 10th Symp. on Advances in Tracer Methodology, New York: Plenum Publ. Corp. 1966.Google Scholar
  5. Kaiser, F., u. W. Schaumann: Stoffwechsel von Derivaten des Helveticosids und Helveticosols. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 262, 87 (1969).CrossRefGoogle Scholar
  6. Kelly, R.G., E.A. Peets, S. Gordon, and D.A. Buyske: Determination of C-14 and H-3 in biological samples by Schöninger combustion and liquid scintillation techniques. Analyt. Biochem. 2, 267 (1961).PubMedCrossRefGoogle Scholar
  7. Lauterbach, F.: Enterale Resorption, biliäre Ausscheidung und enterohepatischer Kreislauf von Herzglykosiden bei der Ratte. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 247, 391 (1964).CrossRefGoogle Scholar
  8. —, u. G. Vogel: Untersuchungen über den enteralen Transport kardiotoner Steroide in vitro und in vivo. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 255, 37 (1966).CrossRefGoogle Scholar
  9. — Die Abhängigkeit der enteralen Wirkungsquote kardiotoner Steroide von der angebotenen Dosis. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 259, 248(1968).CrossRefGoogle Scholar
  10. Megges, R., u. K. Repke: Über Faktoren, welche die orale Wirksamkeit von Herzglykosiden bestimmen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 241, 534 (1961).CrossRefGoogle Scholar
  11. Repke, K., u. I. Herrmann: Speciesunterschiede in der Geschwindigkeit der fermentativen Inaktivierung von Digitoxin. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 243, 331 (1962).CrossRefGoogle Scholar
  12. Schaumann, W., u. R. Wegerle: Verbesserung der Resorption von Helveticosid und Helveticosol durch Substitution der Hydroxylwasserstoffe an der Digitoxose. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 262, 73 (1969).CrossRefGoogle Scholar
  13. Schöninger, E.: Eine mikroanalytische Schnellbestimmung von Halogen in organischen Substanzen. Mikrochim. Acta 1955, 123.Google Scholar
  14. Segel, K.H.: Tritierte Verbindungen. I. Cymarol-(19-3H)(3β, 5β, 14β, 19-Tetraoxycardenol-(19-3H)-D-cymarosid). J. prakt. Chem. 4. Reihe, 13, 152 (1961).CrossRefGoogle Scholar
  15. Shidi, T., T. Higashimura, O. Yamada, and N. Nokara: External standard method for determination of efficiency in liquid scintillation counting. Int. J. appl. Radiat. 13, 308 (1962).CrossRefGoogle Scholar
  16. Wilzbach, K.E.: Advances in Tracer Methodology, pp.4–28. Ed. S. Rothschild.New York: Plenum Press 1963.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1969

Authors and Affiliations

  • F. Zielske
    • 1
    • 2
    • 3
  • W. Voigtländer
    • 1
    • 2
    • 4
  • W. Schaumann
    • 1
    • 2
    • 4
  1. 1.Institut für Nuclearmedizin und spezielle Biophysik im Radiologischen ZentrumMedizinischen Hochschule HannoverDeutschland
  2. 2.ForschungsabteilungenBoehringer Mannheim GmbHDeutschland
  3. 3.Klinikum SteglitzFrauenklinik und -poliklinikBerlin 45Deutschland
  4. 4.Boehringer Mannheim GmbHMannheim 31Deutschland

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