Reduction of erythrocyte membrane permeability and protein binding of low-molecular-weight drugs following glycoside derivitization.

The permeability of glycosides (salicin, arbutin, glycyrritin, p-nitrophenyl-beta-D-glucopyranoside, p-nitrophenyl-beta-D-galactopyranoside, p-nitrophenyl-beta-D-lactopyranoside, and p-nitrophenyl-beta-D-maltopyranoside) and their aglycons through human erythrocyte membrane was investigated. The transport rate of the glycosides through human erythrocyte membrane was slower than that of their aglycons. Glycosides with a disaccharide did not permeate the erythrocyte membrane; this observation suggests that the introduction of disaccharide to drugs gives rise to a significant decrease in the leakage of drugs through the erythrocyte membrane. The derivatives of glycosides encapsulated in erythrocytes were not released from these erythrocytes into the outer medium. The transport capacity of the glycosides was not influenced by the kind of suspending medium, but that of the aglycons was influenced by the medium. The glycosides bound to human serum albumin more weakly than their aglycons. Particularly, the glycosides were more difficult to displace from 7-anilinocoumarin-4-acetic acid (site III drug) than their aglycons, except for glycyrritin.