Absorption of benzoic acid in segmental regions of the vascularly perfusedrat small intestine preparation

Oral bioavailability is a consequence of intestinal absorption, exsorption, and metabolism and is further modulated by the difference in activities am ong segmental regions. The influence of these factors on the net absorption of benzoic acid (BA), a substrate that is metabolized to hippurate and is transported by the monocarboxylic acid transporter 1, was studied in the re circulating, vascularly perfused, rat small intestine preparation. Metaboli sm of BA was not observed for both systemic and intraluminal injections int o segments of varying lengths. But, secretion of BA into lumen was noted. A bsorption of BA (0.166-3.68 mu mol) introduced at the duodenal end for abso rption by the entire intestine was complete (>95% dose at 2 h) and dose-ind ependent, yielding similar absorption rate constants (k(a) of 0.0464 min(-1 )). The extent of absorption remained high (92-96% dose) when BA was inject ed into closed segments of shorter lengths (12 or 20 cm), suggesting a larg e reserve length of the rat intestine. However, k(a) was higher for the jej unum (0.0519 and 0.0564 min(-1), respectively, for the 12- and 20-cm segmen ts) and exceeded that for the duodenum (12-cm segment, 0.0442 min(-1)) and ileum (20-cm segment, 0.0380 min(-1)) at closed injection sites. The findin g paralleled the distribution of monocarboxylic acid transporter isoform 1 detected by Western blotting along the length of the small intestine. Fits of the systemic and oral data (based on duodenal injection for absorption b y the whole intestine) to the traditional, physiological model and to the s egregated flow model (SFM) that describes partial intestinal flow to the en terocyte region showed a better fit with the SFM even though metabolite dat a were absent.