title: Schedule-dependent efficacy of idarubicin (Ida) and doxorubicin (Dox).
abstract: 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.
authors.affiliation: Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263.
authors.forename: H
authors.initials: H
authors.lastname: Minderman
authors.forename: M D
authors.initials: MD
authors.lastname: Buscaglia
authors.forename: Y M
authors.initials: YM
authors.lastname: Rustum
mesh_terms: 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
chemical_list: D004317:Doxorubicin; D015255:Idarubicin