Abstract
Sulfonylureas are the hypoglycemic agents that have been used to treat non-insulin dependent diabetes mellitus patients for decades. Commonly used doses differ to a high extent among sulfonylureas.
Recent studies have shown the presence of a receptor on the plasma membrane of the β-cell specifically binding all these drugs. The binding affinity constant (Kd) of sulfonylureas to its receptor correlates well with their potencies of the induction of insulin secretion. In this study, we investigated the relationship between Kd value and plasma unbound drug concentrations (Cf) after administration of the usual doses of several sulfonylureas in human and obtained a good positive correlation between these two parameters, Kd and Cf.
The calculated receptor occupancy (∅=Cf/(Kd+Cf)×100%) of these drugs showed a constant value (56.7±10.8%) regardless of a wide range of administered doses. It was successful to predict both the therapeutic blood concentrations and usual doses of sulfonylureas, based on the good correlation between Kd value and plasma unbound concentration.
