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Abstract

The secretory intestinal transport of some beta-lactam antibiotics and anionic compounds: a mechanism contributing to poor oral absorption.

H Saitoh, C Gerard and B J Aungst
Journal of Pharmacology and Experimental Therapeutics July 1996, 278 (1) 205-211;
H Saitoh
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C Gerard
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B J Aungst
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Abstract

The mechanisms of intestinal permeation of several beta-lactam antibiotics and anionic compounds were studied in vitro using excised rat intestinal segments. Permeation of cefazolin through jejunum, ileum and colon was highly secretory-oriented; serosal-to-mucosal permeation rates were two- to three-fold greater than mucosal-to-serosal permeation rates. Serosal-to-mucosal permeation decreased in the absence of D-glucose, and mucosal-to-serosal permeation increased, indicating that the preferential secretory transport of cefazolin is energy dependent. Ampicillin permeation across rat jejunum also favored secretion, whereas the permeation of cefaclor and cephradine favored absorption. Because cefazolin is anionic, several structurally unrelated anionic compounds were also tested. Of these only phenol red exhibited preferential serosal-to-mucosal permeation. The intestinal permeation of phenol red was concentration dependent and glucose dependent. Verapamil and a monoclonal antibody to P-glycoprotein only modestly and inconsistently affected the permeation of cefazolin, ampicillin and phenol red. Probenecid and guanidine were much more effective inhibitors of cefazolin and phenol red secretion. Mutual interactions between cefazolin and phenol red were also observed. These results show that the rat intestine has the capability for net secretory transport of some hydrophilic, anionic compounds. Transport of these compounds has some of the characteristics of organic anion and organic cation transport systems.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 278, Issue 1
1 Jul 1996
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Abstract

The secretory intestinal transport of some beta-lactam antibiotics and anionic compounds: a mechanism contributing to poor oral absorption.

H Saitoh, C Gerard and B J Aungst
Journal of Pharmacology and Experimental Therapeutics July 1, 1996, 278 (1) 205-211;

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Abstract

The secretory intestinal transport of some beta-lactam antibiotics and anionic compounds: a mechanism contributing to poor oral absorption.

H Saitoh, C Gerard and B J Aungst
Journal of Pharmacology and Experimental Therapeutics July 1, 1996, 278 (1) 205-211;
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