COMPARISON OF ABSORPTION MECHANISMS OF AMINO-β-LACTAM ANTIBIOTICS, CEFTIBUTEN AND S-1090, A NEW ORALLY ACTIVE ANTIBIOTIC

Abstract

The transport characteristics of cefaclor, ceftibuten and S-1090, a new orally active antibiotic, in rat intestinal brush border membrane vesicles were compared. The uptake of ceftibuten showed a typical overshooting (up-hill) transport in the presence of W-gradient, while only a slightly stimulated uptake was observed in the case of cefaclor or S-1090. Although various types of dipeptides and tripeptides exhibited inhibitory and counter-transport effects on the uptake of ceftibuten, S-1090 uptake was inhibited by the dipeptides possessing cyclic ring in N-terminal amino acid but inhibitory effects were not observed when these amino acid was at C-terminal. Cefaclor, cephalexin and the dipeptides composed of amino acids with aliphatic chain did not show significant inhibitory effects. Countertransport effects on S-1090 uptake were observed in the vesicles preloaded only with histidyl-peptides. The uptake characterictics of these cephems into Caco-2 cells were also separately investigated. From the above results, these oral cephems are considered to be absorbed by dipeptides transport carrier, however, there seems to be the heterogeneity (multiplicity) in dipeptide transport systems which may depend on the structure of N-terminal amino acid.