Comparison of the intracellular pharmacokinetics of doxorubicin and 4'-epi-doxorubicin in patients with acute leukemia.
A direct comparison of the intracellular pharmacokinetics of 4'-epi-doxorubicin and doxorubicin was carried out in five patients with leukemia who were given weekly low doses of a combination of these drugs at 20 mg each in an i.v. injection. Blood samples were collected for 48 h after administration and the drug concentrations in leukemic cells were determined by high-performance liquid chromatography (HPLC). The intracellular peak concentrations of 4'-epi-doxorubicin were higher than those of doxorubicin in all patients. The AUC for the intracellular drug concentration vs time curve was significantly higher for 4'-epi-doxorubicin. The intracellular uptake and retention were also studied in vitro after incubation of isolated leukemic blast cells with the two drugs; they showed the same pattern observed in vivo. We conclude that 4'-epi-doxorubicin and doxorubicin exhibit different pharmacokinetics in malignant cells. The therapeutic significance of this finding requires further evaluation.
Tidefelt
U
U
Department of Medicine, Huddinge Hospital, Sweden.
Sundman-Engberg
B
B
Paul
C
C
D000208:Acute Disease; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D015251:Epirubicin / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D015251:Epirubicin; D004317:Doxorubicin