Pharmacokinetics of daunorubicin after administration as free drug or as DNA complex in leukemic patients.
An earlier whole-body autoradiographic study in mice revealed large differences between the tissue distribution of daunorubicin (D) after administration as free drug as as DNA-linked D. Therefore, the pharmacokinetics of D administered as free drug or linked to DNA was studied in 15 adult patients with acute non-lymphoblastic leukemia. The data obtained following infusion of free drug over either 45 or 240 min could be fitted to a two-compartment open-body model. With the D-DNA infusion considerably higher plasma concentrations were achieved, with a slower distribution and elimination from plasma than seen after the administration of free drug. this confirmed earlier animal data indicating a different pharmacokinetic behavior of D when it was administered linked to DNA. Furthermore, different pharmacokinetic parameters were obtained for D during infusion and in the post-infusion phase after administration of DNA-linked D (P less than 0.005). This finding strongly indicates that the D-DNA acts as a slow-release preparation in humans, which might modify tissue distribution and toxic side-effects of the drug.
D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D003630:Daunorubicin / Q000097:blood / Q000378:metabolism*; D004338:Drug Combinations / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007938:Leukemia / Q000378:metabolism*; D008954:Models, Biological; D013997:Time Factors
D018736:DNA Adducts; D004338:Drug Combinations; C020270:daunorubicin-DNA; D004247:DNA; D003630:Daunorubicin