Effect of adriamycin on CFUGM at plasma concentrations found following therapeutic infusions

Abstract

Summary The effect of adriamycin on human and mouse CFUGM was examined at concentrations and times suggested by plasma clearance data derived from the results of a number of published studies. Our results suggest that the high concentrations of drug present in the plasma for short periods of time following infusion are only weakly cytotoxic towards the CFUGM when incubated for similar times. In contrast, there was a considerably greater cytotoxic effect when the drug was examined at low concentrations for periods similar to those described for the terminal phase of adriamycin clearance. The principal metabolite, adriamycinol, was poorly cytotoxic.

Continuous Infusion or Intravenous Bolus: What Is the Rationale for Doxorubicin Administration?

“…Eichholtz-Wirth (16) has shown that the cytotoxicity of doxorubicin to Chinese hamster and HeLa cells was regularly dependent on exposure time as well as on exposure dose, in the 30-240 min range, although intracellular drug concentration reached a plateau at 60 min. Similarly, Bailey-Wood et al (17) have presented results which suggest that "the high concentrations of drug present in the plasma for short periods of time are only weakly cytotoxic towards the colony-forming units when incubated for similar times", and that, in contrast, "there was a considerably greater cytotoxic effect when the drug was examined at low concentrations for periods similar to those described for the terminal phase of adriamycin clearance". Furthermore, a study by Rupniak et al (18) shows a considerable increase of in vitro sensitivity of ovarian or colon carcinoma cells when the cells are exposed continuously to doxorubicin as opposed to when they are exposed to this drug for 1 h only (Table IV) : in this paper, the ratio of the (9) and Georgoulias et al (13).…”