The differential distribution of doxorubicin (Adriamycin® = AM) and daunorubicin (Daunomycin = DM) within the blood components, after an i.v. injection of 10 or 15 mg/kg of body weight, was investigated in Cd-COBS rats. AM and DM were measured by a fluorimetric procedure, and the unchanged compound was separated from its metabolites and quantified by means of the TLC scanning fluorescence technique. AM accumulated in the following order (of decreasing percentages): plasma and red cells (RBC), white cells (WBC), and platelets (PT), but the absolute amount of drug that reached each cell type was related to its relative volume. In the presence of higher blood concentrations (after injection of 15 mg/kg of body weight) the RBCs accumulated much more AM than the plasma, WBC, and PT; suggesting that the RBC fraction has a greater capacity to concentrate the drug. However, if the concentration of AM is expressed per unit volume of each component, a markedly higher value was observed for PT, and this was confirmed byin vitro results obtained by incubating blood in the presence of AM. DM seemed to be distributed on a percent basis to a greater extent than AM in the RBC fraction. Both compounds were taken up by blood cells, particularly platelets, to levels in excess of the extracellular concentration. This work was supported by NCI (Contract No. NOI CM 67064) and CNR (Progetto Finalizzato: Control of Cancer Growth).
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Beermann B., Hellström K., Lindström B. and Rosén A (1975): Binding-site interaction of chlorthalidone and acetazolamide, two drugs transported by red blood cells.Clin. Pharmacol. Ther., 17, 424–432.
Boullin D.J. and O’Brien R.A. (1969): The accumulation of guanethidine by human blood platelets. Br. J. Pharmacol.,35, 90–102.
Pocelinko R. and Solomon H.M. (1970): Accumulation of debrisoquin-14C by the human platelet.Biochem. Pharmacol., 19, 697–703.
Gaut Z.N. (1973): Binding of cyproheptadine-(N-methyl-l4C) by human blood platelets: Inhibition by phenothiazines and tricyclic antidepressants.J. Pharmacol. Exp. Ther., 185, 171–176.
Da Prada M. and Pletscher A. (1975): Accumulation of basic drugs in 5-hydroxytryptamine storage organelles of rabbit blood platelets.Eur. J. Pharmacol., 32, 179–185.
Solatunturi E. and Ahtee L. (1968): Subcellular distribution of some phenothiazimes in blood platelets of rabbit. J. Pharm. Pharmacol.,20, 289–292.
Kenney D.M., Chao F.C., Tullis J.L. and Conneely G.S. (1975): Colchicine uptake and binding by human platelets.Thromb. Diath. Haemorrb., 34, 780–794.
Weksler B.B., Gillick M. and Pink J. (1977): Effect of propranolol on platelet function. Blood,49, 185–196.
Hornig D., Weber F. and Wiss O. (1971): Studies on the uptake of [I-l4C] ascorbic acid and [I-l4C]-dehydroascorbic acid by platelets of guinea pigs.Clin. Chim. Acta. 33, 187–196.
Ahtee L., Boullin D.J. and Peasonen M.K. (1974): Transport of taurine by normal human blood plateletsBr. J. Pharmacol., 52, 245–251.
Boullin D.J., Votavova M. and Green A.R. (1972): Protein synthesis by human platelets after accumulation of leucine and arginine.Thromb. Diath. Haemorrh., 28, 54–64.
Solomon H.M., Spirt N.M. and Abrams W.B. (1970): The accumulation and metabolism of dopamine by human platelets.Clin, pharmacol. Ther., 11, 838–845.
Hebden H.F., Hadfield J.R. and Beer C.T. (1970): The binding of vinblastine by platelets in the rat.Cancer Res., 30, 1417–1424.
Secret C.J., Hadfield J.R. and Beer C.T. (1972): Studies on the binding of [3H] vinblastine by rat blood platelets «in vitro»: Effects of colchicine and vincristine.Biochem. Pharmacol. 21, 1609–1624.
Creasey W.A., Bensch K.G. and Malawista S.E. (1971): Colchicine, vinblastine and griseofulvin: Pharmacological studies with human leukocytes.Biochem. Pharmacol., 20, 1579–1588.
Lindford J.H., Hryniuk W. and Israels L.G. (1971): Adsorption to human red blood cells of chlorambucil and other biological alkylating agents.Biochem. Pharmacol., 18, 2723–2735.
Huffman D.H. and Bachur N.R. (1972): Daunorubicin metabolism by human hematological components.Cancer Res., 32, 600–605.
Finkel J.M., Knapp K.T. and Mulligan L.T. (1969): Fluorometric determination of serum levels and urinary excretion of daunomycin (NSC-82151) in mice and rats.Cancer Chemother. Rep., 53, 159–164.
Benjamin R.S., Riggs C.E.Jr. and Bachur N.R. (1977): Plasma pharmacokinetics of adriamycin and its metabolites in humans with normal hepatic and renal function.Cancer Res., 37, 1416–1420.
Watson E. and Chan K.K. (1976): Rapid analytic method for adriamycin and metabolites in human plasma by a thin-film fluorescence scanner.Cancer Treat. Rep., 60, 1611–1618.
Israel M., Wilkinson P.M., Pegg W.J. and Frei E. III (1978): Hepatobiliary metabolism and excretion of adriamycin and N-trifluoroacetyladriamycin-14-valerate in the rat.Cancer Res., 38, 365–370.
Duarte-Karim M., Ruysschaert J.M. and Hildebrand J. (1976): Affinity of adriamycin to phospholipids. A possible explanation for cardiac mitochondrial lesions.Biochem. biophys. Res. Commun., 71, 658–663.
Goldman R., Facchinetti T., Bach D., Raz A. and Shinitzky M. (1978): A differential interaction of daunomycin, adriamycin and their derivatives with human erythrocytes and phospholipid bilayers.Biochim. Biophys. Acta, 512, 254–269.
Garattini S. (1978): Platelet-drug interactions: An open field. In: G. de Gaetano and S. Garattini Platelets: A Multidisciplinary Approach, New York, Raven Press, pp. 61–73.
Cline M.J. (1965): Metabolism of the circulating leuhocyte.Physiol. Rev. 45, 674–720.
Fox I.H., Wyngaarden J.B. and Kelley W.N. (1970): Depletion of erythrocyte phosphoribosylpyrophosphate in man.N. Engl. J. Med., 283, 1177–1182.
Chiotto G., Perona G., De Sandre G. and Cortesi S. (1963): Bexokinase and TPN-dependent dehydrogehases of leukocytes in leukemia and other haematological disorders.Br. J. Haematol., 2, 345–350.
Henderson R.J.Jr., Hill F.L. and Mills G.C. (1970): Phosphorylation of tris (hydroxymethyl) aminomethane by human erythrocytes.Arch. Biochem. Biophys., 139, 311–319.
Karnovsky M.L. (1968): The metabolism of leukocytesSemin. Hematology, 5, 156–165.
Miwa S., Tanaka K.R. and Valentine W.N. (1962): Erythrocytic and leuhocytic glycolytic enzyme studies in hematologic and nonhematologic diseases.Acta Haematol Jap., 25, 12–26.
Agam G., Bessler H. and Djaldetti M. (1976): In vitro DNA and RNA synthesis by human platelets.Biochim. Biophys. Acta, 425, 41–48.
Whaun J.M., Dundas J.E. and Clarke H. (1977):Daunomycin and platelet function. Communication presented at the 10th International Congress of Chemotherapy, Zürich, Switzerland, September 18–23.
Federation of the American Societies for Experimental Biology (1964):Biology Data Book, Washington, FASEB p. 269.
Nakeff A. and Ingram M. (1970): Platelet count: Volume relationships in four mammaliam species.J. Appl. Physiol., 28, 530–533.
About this article
Cite this article
Colombo, T., Broggini, M., Garattini, S. et al. Diferential adriamycin® istribution to blood components. European Journal of Drug Metabolism and Pharmacokinetics 6, 115–122 (1981). https://doi.org/10.1007/BF03189477
- Anticancer agents
- pharmacokinetics in rats
- blood cells distribution