EVIDENCE THAT DESFERRIOXAMINE CANNOT ENTER CELLS BY PASSIVE DIFFUSION

Accumulation of [C-14]desferrioxamine by rat visceral yolk sac in vitro has been compared with that of [C-14]sucrose, a probe for fluid-phase pinocytosis. Kinetic parameters for both substrates are closely similar, as are the effects of inhibitors. It is concluded from these data, and from theoretical considerations, that desferrioxamine cannot enter cells other than by pinocytosis and that, once internalized, it will remain in the lysosomes. The results indicate the need for a re-evaluation of the pharmacokinetic mechanisms traditionally accepted for the drug's ability to deplete iron from cells and tissues.