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Research ArticleArticle

Absorption of Benzoic Acid in Segmental Regions of the Vascularly Perfused Rat Small Intestine Preparation

Diem Cong, Angela K. Y. Fong, Ronita Lee and K. Sandy Pang
Drug Metabolism and Disposition December 2001, 29 (12) 1539-1547;
Diem Cong
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Angela K. Y. Fong
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Ronita Lee
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K. Sandy Pang
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Abstract

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.

Footnotes

  • This work was supported by the Medical Research of Canada (MOP36,457); D.C. was a recipient of the Ontario Graduate Scholarship, Canada.

  • Abbreviations used are::
    BA
    benzoic acid
    Mct1
    monocarboxylate transporter isoform 1
    HA
    hippuric acid
    HPLC
    high-pressure liquid chromatography
    PBS
    phosphate-buffered saline
    PMSF
    phenylmethylsulfonyl fluoride
    TBST
    Tris-buffered saline/0.1% Tween 20
    TLC
    thin-layer chromatography
    TM
    traditional physiologically based model
    SFM
    segregated flow model
    ANOVA
    analysis of variance
    ARA
    amount remaining to be absorbed
    • Received April 27, 2001.
    • Accepted September 5, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 29 (12)
Drug Metabolism and Disposition
Vol. 29, Issue 12
1 Dec 2001
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Research ArticleArticle

Absorption of Benzoic Acid in Segmental Regions of the Vascularly Perfused Rat Small Intestine Preparation

Diem Cong, Angela K. Y. Fong, Ronita Lee and K. Sandy Pang
Drug Metabolism and Disposition December 1, 2001, 29 (12) 1539-1547;

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Research ArticleArticle

Absorption of Benzoic Acid in Segmental Regions of the Vascularly Perfused Rat Small Intestine Preparation

Diem Cong, Angela K. Y. Fong, Ronita Lee and K. Sandy Pang
Drug Metabolism and Disposition December 1, 2001, 29 (12) 1539-1547;
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