Binding of cyclosporine by erythrocytes: influence on cell shape and deformability

Abstract

Cyclosporine is a widely used immunosuppressive drug with a high affinity for erythrocytes. It was hypothesized that the hydrophobic agent would interact with the erythrocyte membrane, which could cause a shape change and alter cell deformability. Administration of 300 mg cyclosporine in vivo and incubation of erythrocytes with concentrations up to 100 mg l-1 in vitro at room temperature showed that cyclosporine is found in the cytoplasm, but not in the membrane of erythrocytes and that cell shape or deformability were not affected. Incubation of erythrocytes with the highest cyclosporine concentration (100 mg l-1) at 37 degrees C lead to a time-dependent, slight stomatocytic shape transformation, indicating that the drug is intercalated preferentially into the inner hemileaflet of the membrane under these conditions. Cyclosporine metabolites had no effect on the cell shape. The shape of erythrocyte ghosts was neither affected by cyclosporine nor by its metabolites. It is concluded that cyclosporine is bound in the erythrocyte cytoplasm and does not affect the cell membrane and cell deformability at therapeutic concentrations. These results may contribute to a better understanding of the interactions of cyclosporine with cells.