The effect of salicylic acid on the hypoglycemic activity and blood carbutamide concentration after oral administration of carbutamide was investigated in rabbits. Salicylic acid was found to enhance the hypoglycemic activity, while on the other hand, it was found to deorease the blood carbutamide concentration. Salicylic acid markedly decreased the in vivo binding of carbutamide to rabbit plasma proteins, and caused a significant increase in the plasma concentration of unbound carbutamide, despite a significant decrease in the plasma concentration of total carbutamide. These results lead us to conclude that the displacement of carbutamide from its plasma protein binding sites by salicylic acid produces both the enhanced hypoglycemic activity and the decreased blood carbutamide concentration.
