Secretory mechanisms of grepafloxacin and levofloxacin in the human intestinal cell line Caco-2

Grepafloxacin and levofloxacin transport by Caco-2 cell monolayers was exam ined to characterize the intestinal behavior of these quinolones. The level s of transcellular transport of [C-14]grepafloxacin and [C-14]levofloxacin from the basolateral to the apical side were greater than those in the oppo site direction. The unidirectional transport was inhibited by the presence of excess unlabeled quinolones, accompanied by increased accumulation. The inhibitory effects of cyclosporin A plus grepafloxacin on basolateral-to-ap ical transcellular transport and cellular accumulation of [C-14]grepafloxac in were comparable to those of cyclosporin A alone, indicating that the tra nsport of grepafloxacin across the apical membrane was mainly mediated by P -glycoprotein. On the other hand, basolateral-to-apical transcellular trans port of [C-14]levofloxacin in the presence of cyclosporin A was decreased b y unlabeled levofloxacin, grepafloxacin, and enoxacin, accompanied by signi ficantly increased cellular accumulation. The organic cation cimetidine, or ganic anion p-aminohippurate, and the multidrug resistance-related protein (MRP) modulator probenecid did not affect the transcellular transport of [C -14]grepafloxacin or [C-14]levofloxacin in the presence of cyclosporin A. T he basolateral-to-apical transcellular transport of levofloxacin in the pre sence of cyclosporin A showed concentration-dependent saturation with an ap parent Michaelis constant of 5.6 mM. In conclusion, these results suggested that basolateral-to-apical flux of quinolones was mediated by P-glycoprote in and a specific transport system distinct from organic cation and anion t ransporters and MRP.