Erythrocytes and the transport of drugs and endogenous compounds

This review considers the significance and measurement of endogenous compounds and drugs on erythrocytes. Part I examines literature examples where a direct measurement of hydrocortisone, phenytoin and valproate was performed on unwashed red cells in vitro and in vivo, showing a consistent contribution of the erythrocyte fraction to the transport of these compounds. In vitro partition experiments using systems composed of plasma water, plasma proteins and erythrocytes are discussed. When spiked blood is diluted with blank autologous plasma water, erythrocytes always discharge the compound over-proportionally compared to plasma proteins. In vivo, during the distribution phase, the elimination half-life from the erythrocyte is the same as or shorter than that from plasma water, and substantial amounts of drug leaving the circulation originate from erythrocytes. In Part II, the transfer of compounds is considered and evidence for the facilitated exchange of red cell associated substances between the erythrocyte and capillary endothelium presented. Situations where a failure to analyse the erythrocyte compartment leads to the loss of vital information are identified. Part III explores methods for analysing erythrocyte associated substances, most commonly indirect calculation, or analysis of washed erythrocytes. A direct determination is rarely performed, but one such method, allowing concurrent plasma analysis, is discussed. An instrument collects a fixed and known quantity of a maximally compressed cell mass, without disturbing the equilibrium between cells and plasma. To isolate compounds associated with the mass of erythrocytes, the red cell sediment can often be extracted quantitatively into a blank protein solution.