Intestinal absorption aspect of non-lipophilic low molecular weight drugs: a case of cephalexin and cefazolin.

Abstract

Absorption characteristics of cephalosporins were investigated using in situ recirculation technique. Cephalexin as a fairly well absorbed cephalosporin, and cefazolin as a poorly absorbed one were selected as model compounds. Absorption of cephalexin was much faster in its isoelectric region than in alkaline pH. The pH-absorption profile was not consistent with the pH-partition behavior. The absorption of cephalexin was as much as 4.6 times of cefazolin. This difference could not be explained by the pH-partition hypothesis. The surface activities of cephalosporins were investigated and their contributions to the absorption characteristics were little. The transfer rate of cephalosporins from aqueous lecithin liposome dispersion was investigated. The membrane transfer rate of cephalexin was markedly faster than cefazolin and similar result was obtained when liposome was prepared from rat intestinal total lipids. The pH-profile of the transfer rate of cephalexin across the lipid bilayers was similar to the pH-absorption profile. It is suggested that liposomes prepared from total lipids of the intestine as well as lecithin liposomes are suitable and efficient models for investigation of the transfer of these drug molecules across the intestinal membrane.