Human red blood cells: Rheological aspects, uptake, and release of cytotoxic drugs

The shape of a normal human red blood cell (RBC) is well known: under resting conditions it is that of a biconcave discocyte. However, RBCs can easily undergo transformation to other shapes with stomatocytes and echinocytes as extremes. Various anticancer agents, generally reactive and labile substances, e.g., oxazaphosphorines and fluoropyrimidines, can induce severe deformation of shape. Shape changes in erythrocytes can induce rheological disturbances, which occasionally have pathophysiological. consequences. It is difficult to estimate the impact of shape changes on the in vivo behavior of agents of biological interest. However, it has been demonstrated for various anticancer agents that erythrocytes fulfill an important role in their uptake, transport, and release. Moreover. some anticancer agents are capable of influencing important transporters such as MRP and GLUT-1. Monitoring of erythrocyte concentrations of certain cytotoxic agents is therefore of interest as the data generated can have a predictive outcome for therapeutic efficacy. This is true for cyclophosphamide, ifosfamide, lometrexol, and 6-mercaptopurine, as well as MRP and GLUT-1 mediated agents.