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Serum and tissue concentrations of doxorubicin after IV administration of doxorubicin or doxorubicin-DNA complex to patients with gastrointestinal cancer

  • Original Articles
  • Doxorubicin, Gastrointestinal Cancer
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Summary

Blood and tissue concentrations of doxorubicin (DOX) were assayed after an intraoperative IV test dose of either free DOX 10 mg or its DNA complex 10 mg to patients with gastrointestinal cancer. After administration of the free drug, blood DOX levels decreased in an at least biphasic way, while DOX-DNA gave higher blood concentrations, which decreased slowly with no clear inflexion point on the concentration-time curve within the first hour. Tissue concentrations of DOX did not differ significantly after the two forms of the drug, liver being the tissue with the highest levels, followed by lymph node metastases, tumor tissue, muscle, and normal intestinal mucosa. If skeletal muscle can be used as a substitute for myocardium, lower cardiotoxicity of DOX-DNA than of DOX is not likely to be due to a difference in tissue uptake and retention between the two forms of DOX.

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References

  1. Andersson B, Beran M (1980) Leukemic cell versus plasma levels of daunorubicin and daunorubicinol after infusion of daunorubicin as free drug or the DNA complex. Cancer Chemother Pharmacol 4:205

    Google Scholar 

  2. Baurain R, Deprez-De Campeneere D, Zenebergh A, Trouet A (1982) Plasma levels of doxorubicin after IV bolus injection and infusion of the doxorubicin — DNA complex in rabbits and man. Cancer Chemother Pharmacol 9:93

    Google Scholar 

  3. Benjamin RS, Riggs CE, Bachur NR (1977) Plasma pharmacokinetics of adriamycin and its metabolites in humans with normal hepatic and renal function. Cancer Res 37:1416

    Google Scholar 

  4. Benjamin RS, Mason JW, Billingham ME (1978) Cardiac toxicity of adriamycin-DNA complex and rubidazone: Evaluation by electrocardiogram and endomyocardial biopsy. Cancer Treat Rep 62:935

    Google Scholar 

  5. Chan KK, Cohen JL, Gross JF, Himmelstein KJ, Bateman JR, Tsu-Lee Y, Marlis AS (1978) Prediction of adriamycin disposition in cancer patients using a physiologic, pharmacokinetic model. Cancer Treat Rep 62:1161

    Google Scholar 

  6. Ferrant A, Hulhoven R, Bosly A, Cornu G, Michaux JL, Sokal G (1979) Clinical trials with daunorubicin — DNA and adriamycin-DNA in acute lymphoblastic leukemia of childhood, acute nonlymphoblastic leukemia, and bronchogenic carcinoma. Cancer Chemother Pharmacol 2:67

    Google Scholar 

  7. Gil P, Favre R, Durand A, Iliadis A, Cano JP, Carcassonne Y (1983) Time dependency of adriamycin and adriamycinol kinetics. Cancer Chemother Pharmacol 10:120

    Google Scholar 

  8. Hulhoven R, Sokal G, Harvengt C (1979) Human pharmacokinetics of the daunorubicin-DNA complex. Cancer Chemother Pharmacol 3:243

    Google Scholar 

  9. Lee YTN, Chan KK, Harris PA, Cohen JL (1980) Distribution of adriamycin in cancer patients. Tissue uptakes, plasma concentration after IV and hepatic IA administration. Cancer 45:2231

    Google Scholar 

  10. Levi-Schaffer F, Bernstein A, Meshorer A, Arnon R (1982) Reduced toxicity of daunorubicin by conjugation to dextran. Cancer Treat Rep 66:107

    Google Scholar 

  11. Merski J, Daskal Y, Busch H (1978) Comparison of adriamycin-induced nucleolar segregation in skeletal muscle, cardiac muscle, and liver cells. Cancer Treat Rep 62:771

    Google Scholar 

  12. Paul C, Lönnqvist B, Gahrton G, Lockner D, Peterson C (1981) Reducing the cardiotoxicity of anthracyclines by complex-binding to DNA: Report of three cases. Cancer 48:1531

    Google Scholar 

  13. Peters JH, Gordon GR, Kashiwase D, Acton EM (1981) Tissue distribution of doxorubicin and doxorubicinol in rats receiving multiple doses of doxorubicin. Cancer Chemother Pharmacol 7:65

    Google Scholar 

  14. Peterson C, Paul C, Gahrton G (1981) Anthracycline — DNA complexes as slow release preparations in the treatment of acute leukemia. In: Lewis DH (ed) Controlled release of pesticides and pharmaceuticals. Plenum. New York, pp 49–65

    Google Scholar 

  15. Robert J, Hoerni B, Vrignaud P, Lagarde CA (1983) Earlyphase pharmacokinetics of doxorubicin in non-Hodgkin lymphoma patients. Cancer Chemother Pharmacol 10:115

    Google Scholar 

  16. Terasaki T, Iga T, Sugiyama Y, Hanano M (1982) Experimental evidence of characteristic tissue distribution of adriamycin. Tissue DNA concentration as a determinant. J Pharm Pharmacol 34:597

    Google Scholar 

  17. Trouet A, Deprez-De Campeneere D (1979) Daunorubicin-DNA and doxorubicin — DNA. A review of experimental and clinical data. Cancer Chemother Pharmacol 2:77

    Google Scholar 

  18. Trouet A, Deprez-De Campeneere D, De Duve C (1972) Chemotherapy through lysosomes with a DNA — daunorubicin complex. Nature New Biol 239:110

    Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Sabbatsbergs Hospital, Box 6401, S-11382, Stockholm, Sweden

    Peter Gunvén & Nils Olof Theve

  2. Department of Pharmacology, Karolinska Institute, Box 60 400, S-10401, Stockholm, Sweden

    Curt Peterson

Authors
  1. Peter Gunvén
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  2. Nils Olof Theve
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  3. Curt Peterson
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Additional information

The work described in this paper was supported by grants from the Swedish Medical Research Council, the Swedish Cancer Society and the Cancer Society in Stockholm

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Gunvén, P., Theve, N.O. & Peterson, C. Serum and tissue concentrations of doxorubicin after IV administration of doxorubicin or doxorubicin-DNA complex to patients with gastrointestinal cancer. Cancer Chemother. Pharmacol. 17, 153–156 (1986). https://doi.org/10.1007/BF00306745

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  • DOI: https://doi.org/10.1007/BF00306745

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