Plasma levels of doxorubicin after IV bolus injection and infusion of the doxorubicin-DNA complex in rabbits and man. Comparison with free doxorubicin.
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.
D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000378:metabolism; D018736:DNA Adducts; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood* / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007700:Kinetics; D011817:Rabbits
D018736:DNA Adducts; C031902:doxorubicin-DNA; D004317:Doxorubicin; D004247:DNA