PH-DEPENDENT TRANSEPITHELIAL TRANSPORT OF CEPHALEXIN IN RABBIT INTESTINAL-MUCOSA

Previous studies have demonstrated carrier-mediated cephalexin (CPX) transport in rat jejunum under basal conditions. The purpose of this study was to compare fluxes of cephalexin (CPX) and benzylpenicillin (BZP) across rabbit intestine to those reported in rat intestine, to determine whether these fluxes exhibit regioselectivity and to investigate the pH dependence of these fluxes. Fluxes of CPX were examined in rabbit jejunal, ileal and distal colonic mucosa in Ussing chambers. Concurrently, transepithelial (TE) potential difference, TE electrical conductance and mannitol fluxes were determined to evaluate tissue viability and integrity. Mucosal (m)-to-serosal(s) fluxes of CPX were approximately 3-times the s-to-m fluxes (0.66 vs 0.18% h-1 3 cm-2, respectively) in both jejunum and ileum under short-circuit conditions. Distal colonic m-to-s and s-to-m fluxes were approximately 0.18% h-1 3 cm-2. Inhibition of Na+/K+-ATPase activity with ouabain or incubation with the Na+/H+ exchange inhibitor, amiloride, reduced by 70 and 40%, respectively, the m-to-s fluxes of CPX in the ileum. Effects of changes in luminal pH on TE transport of CPX and mannitol were studied in ileal and colonic mucosa. At a luminal pH of 5.5, ileal m-to-s transport of CPX was increased to 2.85 +/- 0.12% h-1 3 cm-2 while mannitol flux and electrical properties were unchanged. In distal colon, pH 5.5 in the luminal bathing solution did not alter CPX or mannitol fluxes. pH dependent carrier-mediated transport was not exhibited by BZP. Thus CPX appears to be absorbed by a pH dependent, carrier-mediated mechanism confined to the small intestine whereas BZP absorption appears to occur by an entirely passive process.