1988 年 108 巻 4 号 p. 345-349
The effect of probenecid on the plasma concentration and tissue distribution of sulfadimethoxine (SDM) was examined by using fast and slow acetylator rabbits. The intravenously co-administered probenecid significantly increased the tissue distribution of SDM in fast acetylator rabbits, resulting in the reduction of plasma concentration of SDM. On the other hand, the intravenously co-administered probenecid had no effect on the plasma concentration and tissue distribution of SDM in slow acetylator rabbits. Furthermore, the intravenous co-administration of N4-acetylsulfadimethoxine, which is a major metabolite of SDM and strongly displaces SDM from its serum protein binding sites, significantly increased the tissue distribution of SDM in fast acetylator rabbits, resulting in the reduction of plasma concentration of SDM. These findings indicate that the acetylation capacity for SDM is an important factor determining the effect of probenecid on the plasma concentration and tissue distribution of SDM in rabbits.