Uptake of chloroquine by human erythrocytes.

Analysis of studies of the pH dependence of the kinetics of chloroquine (CQ) uptake by human erythrocytes indicates that the unionised CQ species is the major membrane permeant at physiological pH even though the concentration of this species as a fraction of the total CQ concentration in solution is extremely small (0.01% at pH 7.4). CQ concentration-dependence studies and studies performed in the presence of various substrates and inhibitors of erythrocyte membrane transport failed to provide evidence of saturation or inhibition of CQ transport, which suggests that the likely mechanism of CQ transport across human erythrocyte membranes is by passive diffusion. Results of equilibrium binding studies of CQ to intact and lysed human erythrocytes indicated that the mechanism of CQ accumulation in intact human erythrocytes appears to be by a combination of ion trapping (a consequence of the basic nature of the drug and the pH gradient across the human erythrocyte membrane) and binding of CQ to cell components.