Summary
The distribution of digoxin, digitoxin and ouabain between plasma and erythrocytes in the blood of different species was investigated. In man, cattle, dog, guinea-pig, cat and rat the ratios between erythrocytes and plasma were 0.90, 0.86, 0.90, 0.97, 2.32, 3.50 respectively for digoxin, 0.09, 0.19, 0.11, 0.21, 0.31, 0.26 respectively for digitoxin, and 0.03, 0.09, 0.01, 0.09, 0.09, 0.04 respectively for ouabain.
When buffer solution was used instead of plasma these ratios changed only for digitoxin. The values for human, bovine and rat erythrocytes were 1.37, 1.25 and 2.87 respectively. These changes are most likely to be due to the strong binding of digitoxin to the plasma proteins. The percentage of unbound digitoxin in the plasma was 6.1 in man, 13.1 in cattle and 7.5 in rats.
The greater uptake of digoxin by rat erythrocytes depended mainly upon its high affinity for rat hemoglobin and also on its attachment to membrane constituents.
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References
Betke, K., Kleihauer, E.: Einschleusung von Fremdhämoglobin in Erythrozyten. Folia haemat.83, 69 (1964).
—, Savelsberg, W.: Stufenphotometrische Hämoglobinbestimmung mittels Cyanhämiglobin. Biochem. Z.320, 431 (1950).
Chandrasekhar, N.: Minor proteins in human erythrocytes. Canad. J. Biochem.39, 1489 (1961).
Deutieke, B., Gruber, W.: Anion permeability of mammalian red blood cells: Possible relation to membrane phospholipid patterns. Biochim. biophys. Acta (Amst.)211, 369 (1970).
DeGier, J., Deenen, L. L. M. van, Senden, K. G. van: Glycerol permeability of erythrocytes. Experientia (Basel)22, 20 (1966).
—, Mandersloot, J. G., Deenen, L. L. M. van: Lipid composition and permeability of liposomes. Biochim. biophys. Acta (Amst.)150, 666 (1968).
Jung, F.: Diskussionsbermerkung zu Betke und Kleihauer. Folia haemat.83, 69 (1964).
Kuschinsky, K.: Über die Bindungseigenschaften von Plasmaproteinen für Herzglykoside. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.262, 388 (1969).
—: The specifity of binding of some cardenolides to human serum albumin. Arzneimittel-Forsch. (Drug Res.)20, 842 (1970).
Lepke, S., Passow, H.: Effects of fluoride on potassium and sodium permeability of the erythrocyte membrane. J. gen. Physiol.51, 365 (1968).
Lukas, D. S., DeMartino, A. G.: Binding of Digitoxin and some related cardenolides to human plasma proteins. J. clin. Invest.48, 1041 (1969).
Lüllmann, H., Peters, T., Zwieten, P. A. van: The distribution of3H-labelled cardenolides between isolated guinea-pig atrial tissue and circulating, oxygenated whole blood. Brit. J. Pharmacol.36, 276 (1969).
Nelson, G. L.: Lipid composition of erythrocytes in various mammalian species. Biochim. biophys. Acta (Amst.)144, 221 (1967).
Paganelli, C.V., Solomon, A. K.: The rate of exchange of tritiated water across the human red cell membrane. J. gen. Physiol.41, 259 (1957).
Passow, H.: In: Laboratory techniques in membrane biophysics, p. 21. Ed. H. Passow and R. Stäpfli, Berlin-Heidelberg-New York: Springer 1969.
Riecker, G., Bubnoff, M. von: Die intracellulare Plasmamenge im Erythrozytensediment. Z. ges. exp. Med.132, 102 (1959).
Schanker, L. S., Johnson, J. M., Jeffrey, J. J.: Rapid passage of organic anions into human red cells. Amer. J. Physiol.207, 503 (1964).
—, Nafpliotis, P. A., Johnson, J. M.: Passage of organic bases into human red cells. J. Pharmacol. exp. Ther.133, 325 (1961).
Scholtan, W., Schlossmann, K., Rosenkranz, H.: Bestimmung der Eiwei\bindung von Digitalis-Präparaten mittels der Ultrazentrifuge. Arzneimittel-Forsch. (Drug Res.)16, 109 (1966).
Solomon, A. K.: The permability of the human erythrocyte to sodium and potassium. J. gen. Physiol.36, 57 (1953).
—: Red cell membrane structure and ion transport. J. gen. Physiol.43 (Suppl.), 1 (1960).
—: Characterization of biological membranes by equivalent pores. J. gen. Physiol.51, 5 (1968).
Spratt, J. L., Okita, G. T.: Protein binding of radioactive Digitoxin. J. Pharmacol. exp. Ther.124, 109 (1958).
Witzgall, H., Boyens, H.: Die Bedeutung der Bindung an Albumin, Körperzellen und Bakterien für Pharmakodynamik und Wirkung von Arzneistoffen. Arch. int. Pharmacodyn.148, 511 (1964).
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We wish to acknowledge the skillful technical assistance of Mrs. B. Dalichow and Mrs. K. Schulz.
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Abshagen, U., Kewitz, H. & Rietbrock, N. Distribution of digoxin, digitoxin and ouabain between plasma and erythrocytes in various species. Naunyn-Schmiedebergs Arch. Pharmak. 270, 105–116 (1971). https://doi.org/10.1007/BF00997082
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DOI: https://doi.org/10.1007/BF00997082