Restricted intestinal absorption of some beta-lactam antibiotics by an energy-dependent efflux system in rat intestine.

PURPOSE: The purpose of this study was to examine factors limiting the intestinal absorption of orally inactive beta-lactam antibiotics.
METHODS: Permeation behaviors of various beta-lactam antibiotics across rat intestinal segments were evaluated in vitro using diffusion cells.
RESULTS: Poorly absorbed beta-lactam antibiotics, like cephaloridine and cefoperazone, commonly exhibit greater serosal-to-mucosal permeation than mucosal-to-serosal permeation, while cephalexin permeation was greater in the mucosal-to-serosal direction. In the absence of D-glucose, secretory-oriented permeation of cephaloridine and cefoperazone disappeared. Addition of sodium azide into an experimental buffer including D-glucose significantly and selectively enhanced mucosal-to-serosal permeation of cephaloridine and cefoperazone. Although benzylpenicillin, ampicillin, and amoxicillin all showed secretory-oriented permeation, the tendency to permeation was greatest with benzylpenicillin and least with amoxicillin. Probenecid stimulated mucosal-to-serosal permeation of cephaloridine, but verapamil and p-aminohippuric acid had no significant effect on it.
CONCLUSIONS: It has been suggested that mechanisms which induce secretory-oriented permeation of orally inactive beta-lactam antibiotics are factors limiting intestinal absorption of such antibiotics. This energy-demanding efflux system was distinct from P-glycoprotein-mediated transport. A free alpha-amino group in the molecule is an important factor for reducing an affinity with the efflux system.