Characterization of aminocephalosporin transport across rat small intestine.

Abstract

The absorption mechanism of aminocephalosporins was investigated in rat small intestine. Cephalosporins chosen in this study were cephalexin, cephradine, SCE-100, cefroxadin, cefatrizine, and cefadroxil. Absorption experiments were carried out by both in situ and in vitro techniques. In situ recirculation experiments through the whole small intestine demonstrated that the absorption rates of the antibiotics were saturable (except cephalexin) and inhibited by the short-term pretreatment of the intestinal mucosa with a low concentration of HgCl2, suggesting the participation of proteins and/or sulfhydryl groups within the brush border membrane. Among the tested antibiotics, cefadroxil showed the highest absorption, , in spite of its lowest lipophilicity, and its absorption was inhibited by the simultaneous perfusion of other aminocephalosporins and aminopenicillins. So, the carrier system for cefadroxil seems to be common, at least in part, to amino-β-lactam antibiotics. Also, comparison of the apparent directional permeabilities of the jejunum and ileum by using the everted sacs and noneverted ones in vitro indicated that this drug penetrates more rapidly from mucosa to serosa (M-to-S) than from serosa to mucosa (S-to-M) in both segments. The (M-to-S)/(S-to-M) ratios at the concentration of 0.1 mM were 2.26 and 4.82 in the jejunum and ileum, respectively. The M-to-S flux of the drug was saturable, Na+-dependent, and inhibited by 2, 4-dinitrophenol Thus, it is suggested that energy is required for M-to-S cefadroxil transport. The location of SH-groups of the brush border membrane essential for cefadroxil transport was discussed.