抄録
Rat small intestinal absorption of p-aminobenzoic acid (PABA) was investigated using the in situ recirculating and loop method. The disappearance of PABA from the lumen followed apparent first-order kinetics at lower initial concentration (10-5 M), but showed a distributive phase at higher concentration (10-3 M). A significant amount of p-acetamidobenzoic acid (Ac-PABA), the metabolite of PABA in the intestinal epithelial cell, was found in the intestinal lumen. The appearance of Ac-PABA in the lumen was dose dependent. At 10-5 M PABA, more than 50% of dose was found in the lumen as Ac-PABA and at 10-3 M PABA, nearly 10% of dose was found in the lumen as Ac-PABA after recirculation for 60 min. The induction of the distributive phase at higher dose could be ascertained by the analog computer simulation containing non-linear function. At higher dose, the enzyme in the intestinal mucosa was capacity limited and the free drug was accumulated in the cell and the distributive phase occurred. The appearance of metabolites in the lumen was also observed for p-aminosalicylic acid and p-aminohippuric acid. In addition, the disappearance of acetylated drugs from the lumen was much slower than the parent drugs. These observations suggested the metabolism of drugs in the intestine contributed significantly to the overall first-pass effect and also affected the absorption kinetics of drugs.
