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. Fo r Dox, repeated exposure to the IC30 (d x 3) resulted in comparable su rvival as single exposure to the total accumulative dose (20%). For Id a, repeated exposure to the IC30 (d x 3) decreased survival to 5%, whi le single exposure to the total accumulative dose reduced survival onl y to 20%. Total cellular accumulation of Dox was independent of schedu le of exposure, while for Ida, repeated exposure resulted in a signifi cantly higher drug accumulation compared to the single exposure to the accumulative dose. The data indicate that the schedule-dependent diff erences in cytotoxicity for the two compounds can be accounted for alm ost exclusively by an increased cellular uptake and retention of Ida w ith repeated drug exposure.