Summary
The relative distribution of adriamycin to plasma and blood cells after IV injection of 10 mg/kg was investigated in CD rats bearing intramuscular 256 Walker carcinosarcomas 15 days old. The drug was measured by a fluorimetric procedure and the amount of unchanged compound was separated from metabolites and quantitated by means of a TLC scanning fluorescence technique. In the presence of a tumor much lower hematocrit values are found, with marked anemia and thrombocytopenia associated with leukocytosis. These modified hematologic parameters account for an altered pattern of drug distribution. The low number of blood cells per milliliter results in a smaller amount of drug being present in the cellular fraction, so that more of the compound (even twice as much) is made available in plasma. Changes in adriamycin concentrations per unit volume or cell of each cell type are inversely related to changes in their relative number per milliliter. The only cell fraction where the drug increase per cell or cubic micrometer does not compensate the marked reduction in cell count observed in the presence of tumor is the platelet fraction, in which adriamycin amounts are 25% or less of those observed in the blood of normal rats, indicating that these blood cells become saturated in tumor-bearing animals.
This is a preview of subscription content, log in via an institution to check access.
References
Bell E, Bulbrook RD, Deshpande N (1967) Transcortin in the plasma of patients with breast cancer. Lancet 2: 395
Benjamin RS, Riggs CE Jr, Bachur NR (1977) Plasma pharmacokinetics of adriamycin and its metabolites in humans with normal hepatic and renal function. Cancer Res 37: 1416
Dinh B-L, Brassard A (1968) Renal lesions associated with the Walker 256 adenocarcinoma in the rat. Br J Exp Pathol 49: 145
Donelli M-G, Colombo T, Broggini M, Garattini S (1977) Differential distribution of antitumor agents in primary and secondary tumors. Cancer Treat Rep 61: 1319
Federation of American Societies for Experimental Biology (1964) Biology Data Book. FASEB, Washington, p 269
Finkel JM, Knapp KT, Mulligan LT (1969) Fluorometric determination of serum levels and urinary exretion of daunomycin (NSC 82151) in mice and rats. Cancer Chemother Rep 53: 159
Garattini S, Mor G, Murelli B (1956) Comportamento delle proteine e delle lipoproteine seriche nel ratto portatore di carcinosarcoma di Walker. G Ital Chemioter 3: 68
Hebden HF, Hadfield JR, Beer CT (1970) The binding of vinblastine by platelets in the rat. Cancer Res 30: 1417
Huffman DH, Bachur NR (1972) Daunorubicin metabolism by human hematological components. Cancer Res 32: 600
Kato R, Takanaka A, Takahashi A, Onoda K (1968) Drug metabolism in tumor-bearing rats. Jpn J Pharmacol 18: 224
Marc V, Donelli MG, Bartosek I, Guaitani A, Standen S, Morselli PL (1974) Metabolism of exogenous cortisol in tumor bearing rats. Eur J Cancer 10: 437
Nakeff A, Ingram M (1970) Platelet count volume relationships in four mammalian species. J Appl Physiol 28: 530
Rosso R, Donelli MG, Franchi G, Garattini S (1971) Impairment of drug metabolism in tumor-bearing animals. Eur J Cancer 7: 565
Watson E, Chan KK (1976) Rapid analytic method for adriamycin and metabolites in human plasma by a thin-film fluorescence scanner. Cancer Treat Rep 60: 1611
Wilson JT (1968) An investigation of the decrease in the metabolism of hexobarbital, aminopyrine and p-nitrobenzoic acid by liver from rats bearing a pituitary mammotropic tumor. J Pharmacol Exp Ther 160: 179
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Broggini, M., Colombo, T., Garattini, S. et al. Influence of tumor on adriamycin concentration in blood cells. Cancer Chemother. Pharmacol. 4, 209–212 (1980). https://doi.org/10.1007/BF00254021
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00254021