Schedule-dependent efficacy of idarubicin (Ida) and doxorubicin (Dox).
Schedule dependency of idarubicin (Ida) and doxorubicin (Dox) toxicity was investigated in vitro using the K562 human leukemia cell line. For Dox, repeated exposure to the IC30 (d x 3) resulted in comparable survival as single exposure to the total accumulative dose (20%). For Ida, repeated exposure to the IC30 (d x 3) decreased survival to 5%, while single exposure to the total accumulative dose reduced survival only to 20%. Total cellular accumulation of Dox was independent of schedule of exposure, while for Ida, repeated exposure resulted in a significantly higher drug accumulation compared to the single exposure to the accumulative dose. The data indicate that the schedule-dependent differences in cytotoxicity for the two compounds can be accounted for almost exclusively by an increased cellular uptake and retention of Ida with repeated drug exposure.
Minderman
H
H
Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263.
Buscaglia
M D
MD
Rustum
Y M
YM
D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D005434:Flow Cytometry; D006801:Humans; D015255:Idarubicin / Q000633:toxicity*; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004317:Doxorubicin; D015255:Idarubicin