Effects of total plasma concentration and age on tolbutamide plasma protein binding.

Tolbutamide plasma protein binding at different total tolbutamide concentrations was determined in 44 healthy, nonsmoking, drug-free men from 23 to 87 yr old. The data showed that unbound drug increased with total tolbutamide plasma concentration and with age, but that neither the binding equilibrium constant nor the number of binding sites correlated with age. The increase in unbound fraction with age could be partially explained by the decrease in albumin concentration in elderly subjects. Results of multiple linear regression analysis indicated that, although age had a considerably greater influence than albumin concentration, total tolbutamide concentration was the most important determinant of the unbound fraction. Thus, both age and total plasma concentration may affect tolbutamide kinetics.