Abstract

The transepithelial transport of three fluoroquinolones, norfloxacin, ciprofloxacin and pefloxacin has been compared by using cultured human intestinal Caco-2 cell-layers. Absorptive (apical-basal) fluxes of ciprofloxacin and norfloxacin are small relative to basal to apical fluxes. Norfloxacin and ciprofloxacin are thus subject to active transepithelial secretion. Active net secretion of norfloxacin displays saturation kinetics with Vmax and Km values of 36.2 +/- 6.9 nmol.cm-2.hr-1 and 1.42 +/- 0.79 mM. In contrast, transepithelial pefloxacin fluxes are large, show marked saturation while the direction of net flux is variable and small relative to transepithelial fluxes. Norfloxacin, pefloxacin and ciprofloxacin are all subject to accumulative transport across the basal surface of Caco-2 cell layers. A number of 4-quinolones and fluoroquinolones are capable of inhibition of both net secretion of ciprofloxacin and cellular accumulation across the basal-lateral cell surface. Cinoxacin, a 4-quinolone may selectively inhibit exit from the cell across the apical membrane. Cross-competition studies suggest that fluoroquinolones may compete for a common carrier at the basal-lateral membrane. It is likely that the mechanism of transepithelial secretion involves a common accumulative transport at the basal-lateral membrane followed by facilitated exist across the apical membrane. Pefloxacin may interact with a brush-border carrier for which norfloxacin and ciprofloxacin are poor substrates, enhancing the absorptive flux of this fluoroquinolone.