The role of an α-amino group on interaction with the intestinal and renal peptide carriers (PEPT 1 and PEPT 2, respectively) has been the subject of much investigation. Studies have differed in their conclusions about the role of an α-amino group on carrier-mediated absorption. Most studies have used brush-border membrane vesicles or perfused intestinal segments. These techniques enable the determination of membrane uptake and luminal disappearance, respectively, but not transepithelial transport. Transepithelial transport should be more predictive of absorption because it includes basolateral efflux, which could be the rate-limiting process in drug absorption. The objective of this study was to evaluate the influence of an α-amino group on PEPT 1-mediated transepithelial transport in Caco-2 cells.

The apical-to-basolateral permeability coefficients of cephalosporins with or without a free α-amino group were determined in the presence and absence of a pH gradient. Permeability coefficients obtained under these conditions were used to calculate a permeability ratio (i.e. Papp (pH 6.0)/Papp (pH 7.4)), which should indicate whether PEPT 1 is involved in transport. For cephalosporins with an α-amino group (cephalexin, cefaclor, cefadroxil, cephradine, cephaloglycin) the permeability ratios ranged between 1.77 and 2.77. In contrast, the permeability ratios for cephalosporins without an α-amino group were 1 (approx.; range = 0.74–1.26).

These data suggest that the presence of an α-amino group on cephalosporins increases their PEPT 1-mediated transepithelial transport in Caco-2 monolayers.