Effect of Simultaneous Administration of Drugs on Absorption and Excretion. XV. Effect of Probenecid on Plasma Protein Binding of Sulfadimethoxine in Rabbits : The Role of N^4-Acetylsulfadimethoxine, the Major Metabolite of Sulfadimethoxine

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The effect of probenecid on the plasma protein binding of sulfadimethoxine (SDM) was investigated in rabbits. Probenecid markedly reduced the in vivo binding of SDM to rabbit plasma proteins. On the other hand, probenecid had no effect on the in vitro binding of SDM to rabbit plasma proteins. Probenecid significantly increased N^4-acetylsulfadimethoxine (N^4-AcSDM) concentration in plasma after intravenous bolus injection of SDM, and prolonged the elimination half-life of N^4-AcSDM after intravenous bolus injection of N^4-AcSDM. In addition, N^4-AcSDM reduced the in vitro binding of SDM to rabbit plasma proteins. These results indicate that probenecid indirectly reduces the in vivo binding of SDM to rabbit plasma proteins, by causing a significant increase of N^4-AcSDM concentration in plasma.
社団法人日本薬学会の論文
1983-01-25