Intestinal elimination of p-nitrophenol in the rat

The intestinal metabolism and metabolite transport of p-nitrophenol (PNP), as a model compound have been investigated in an in vivo isolated intestinal loop preparation in the rat. Different PNP concentrations (20 microM, 100 microM and 500 microM) were recirculated to determine the formation and transport of PNP-metabolites (PNP-glucuronide: PNP-G and PNP-sulphate: PNP-S) in the jejunal loop. It was found that the jejunum of the rat was able to metabolize PNP rapidly and to transport the metabolites efficiently back into the luminal solution. About 21, 16 and 6% of recirculated amount of PNP could be detected in 90 minutes as PNP-G in the lumen of jejunal loop when 20, 100 or 500 microM PNP was perfused. These results show that the luminal appearance of PNP-G tended to saturability. Sulphate conjugate of PNP was undetectable in the intestinal lumen at 20 and 100 microM PNP concentrations and PNP-S amounted to 0.07% of recirculated amount of PNP when it was used in a concentrations of 500 microM. These results indicate that the intestinal metabolism and the excretion of metabolites may play a role in the elimination of xenobiotics containing phenolic hydroxyl groups and that the small intestine of the rat forms predominantly PNP-G after luminal administration of PNP.