Effect of Simultaneous Administration of Drugs on Absorption and Excretion. XVII. In Vivo Protein Binding Interaction between Sulfamethoxazole and Chloral Hydrate in Rabbits

Abstract

The effect of chloral hydrate (CH) on the in vivo and in vitro binding of sulfamethoxazole (SMX) to plasma proteins was investigated in rabbits. CH clearly reduced the in vivo binding of SMX to plasma proteins. On the other hand, CH had no effect on the in vitro binding of SMX to plasma proteins. CH was found to indirectly reduce the in vivo plasma protein binding of SMX through the formation of trichloroacetic acid (TCA), which is a major metabolite of CH. In addition, CH was found to indirectly reduce the in vivo plasma protein binding of SMX by causing a significant increase in the plasma concentration of N⁴-acetylsulfamethoxazole (N⁴-AcSMX), which is the major metabolite of SMX and which markedly reduces the in vitro binding of SMX to plasma proteins. These results lead us to conclude that both TCA and N⁴-AcSMX play an important role in the in vivo protein binding interaction betwen SMX and CH in rabbits.