A hypothesis concerning the effect of changes in scheduling upon the cardiotoxicity of adriamycin

Evidence is accumulating that the cardiotoxicity of adriamycin is a function of not only total dosage but of scheduling, with those schedules associated with low peak plasma levels of the drug being associated with significant decrease in cardiac toxicity. It is believed that adriamycin enters the cell by passive diffusion, and most cells studied, both normal and neoplastic, have an active excretory mechanism that pumps adriamycin out of the cell. If it is assumed that the myocardium has such a pump then it can be shown pharmacokinetically that those schedules associated with a low peak plasma level can, under certain circumstances, selectively protect the myocardium.