PT  - JOURNAL ARTICLE
AU  - Diem Cong
AU  - Angela K. Y. Fong
AU  - Ronita Lee
AU  - K. Sandy Pang
TI  - Absorption of Benzoic Acid in Segmental Regions of the Vascularly Perfused Rat Small Intestine Preparation
DP  - 2001 Dec 01
TA  - Drug Metabolism and Disposition
PG  - 1539--1547
VI  - 29
IP  - 12
4099  - http://dmd.aspetjournals.org/content/29/12/1539.short
4100  - http://dmd.aspetjournals.org/content/29/12/1539.full
SO  - Drug Metab Dispos2001 Dec 01; 29
AB  - Oral bioavailability is a consequence of intestinal absorption, exsorption, and metabolism and is further modulated by the difference in activities among 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 recirculating, vascularly perfused, rat small intestine preparation. Metabolism of BA was not observed for both systemic and intraluminal injections into segments of varying lengths. But, secretion of BA into lumen was noted. Absorption of BA (0.166–3.68 μmol) introduced at the duodenal end for absorption by the entire intestine was complete (>95% dose at 2 h) and dose-independent, yielding similar absorption rate constants (ka of 0.0464 min−1). The extent of absorption remained high (92–96% dose) when BA was injected into closed segments of shorter lengths (12 or 20 cm), suggesting a large reserve length of the rat intestine. However,ka was higher for the jejunum (0.0519 and 0.0564 min−1, respectively, for the 12- and 20-cm segments) 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 finding 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 by the whole intestine) to the traditional, physiological model and to the segregated flow model (SFM) that describes partial intestinal flow to the enterocyte region showed a better fit with the SFM even though metabolite data were absent. The American Society for Pharmacology and Experimental Therapeutics