Summary
When injected rapidly IV into rabbits, the plasma levels of free DOX decreased biphasically and the drug was distributed in a volume greater than the body volume. When given as a DNA complex, the area under the concentration versus time curve was increased 10-fold and the distribution volume reduced more than 100-fold. The DOX-DNA complex infused both in rabbits and in human patients reached steady state-concentrations 10 and 20 times higher, respectively, than free DOX infusion, and the distribution volumes were reduced accordingly. These results confirm that the observed lower cardiotoxicity of the DOX-DNA complex arises despite higher plasma concentrations of the drug.
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Bauram, R., Campeneere, D.DD., Zenebergh, A. et al. Plasma levels of doxorubicin after IV bolus injection and infusion of the doxorubicin-DNA complex in rabbits and man. Cancer Chemother. Pharmacol. 9, 93–96 (1982). https://doi.org/10.1007/BF00265386
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DOI: https://doi.org/10.1007/BF00265386