Effect of Simultaneous Administration of Drugs on Absorption and Excretion. XIII. Effect of Salicylic Acid on the Absorption, Distribution and Elimination of Carbutamide in Rabbits

Abstract

Salicylic acid reduced the in situ intestinal absorption of carbutamide, and enhanced the in situ intestinal exsorption of carbutamide. Salicylic acid, however, did not affect the in vitro intestinal absorption of carbutamide. These findings indicate that the displacement of carbutamide from its plasma protein binding sites by salicylic acid can become an important factor affecting the intestinal absorption of carbutamide in intact rabbits. Salicylic acid caused a significant increase in the apparent volume of distribution (V^αβ) and in the total body clearance (Cl_T) of carbutamide. In addition, salicylic acid was found to significantly increase the distribution of carbutamide into the pancreas and into the kidney. These findings may be explained on the basis of the displacement of carbutamide from its plasma protein binding sites by salicylic acid.