Kinetics of daunomycin in leukemia cells and leukocytes in vivo in the rat.
The capability of nucleated blood cells and leukemic cells to transport daunomycin (DNR) to target tissues in the body was investigated in the rat. The in vivo distribution kinetics of DNR entrapped in leukemia cells (brown Norway acute myeloid leukemia, BNML) or in nucleated bone marrow cells, which had been exposed to DNR (0.2 mg/5 X 10(7) cells) in vitro, were determined. It was found that BNML leukemia cells and normal bone marrow cells take up DNR according to a linear pattern up to 400 micrograms/5 X 10(7) cells. When these DNR loaded cells are infused into the rat, dose dependent distribution kinetics are observed. Compared to i.v. injection of the same dosage, cell-bound DNR leads to a higher concentration and a higher tissue area under the curve of DNR in the liver (P less than 0.05) and the spleen (P less than 0.05), while equal levels are attained in bone marrow. Lower concentrations and area under the curve of DNR are observed in cardiac tissue of normal rats (P less than 0.001) and leukemic rats (P less than 0.05). It is concluded that DNR entrapped into marrow and leukemia cells follows different kinetics from free DNR in plasma.
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D003630:Daunorubicin / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D013154:Spleen / Q000378:metabolism
D003630:Daunorubicin