[Displacing effect of serum protein binding on intestinal absorption of sulfadimethoxine]

The displacing effect of serum protein binding on the intestinal absorption of sulfadimethoxine (SDM) in rabbits was examined by using N4-acetylsulfadimethoxine (N4-AcSDM), a major metabolite of SDM, as a displacing drug. N4-AcSDM markedly decreased the in vitro serum protein binding of SDM, while many drugs including phenylbutazone and salicylic acid did not display such a marked decreasing-effect. The intravenous administration of N4-AcSDM clearly decreased the in situ intestinal absorption of SDM. As expected, the intravenously administered N4-AcSDM enhanced the serum concentration of unbound SDM in the common jejunal vein. However, the intravenously administered N4-AcSDM caused no change in the transfer of SDM across the intestinal membrane. These results indicate that the displacement of serum protein binding can become one of factors decreasing the intestinal absorption of SDM.