Transport of levofloxacin in the OK kidney epithelial cell line: Interaction with p-aminohippurate transport

Purpose. To evaluate the mechanism of renal transport of quinolone antibact erial drugs, we examined the interaction of levofloxacin with p-aminohippur ate (PAH) transport systems and the transport of levofloxacin in renal epit helial cells. Methods. Transport of [C-14]PAH or [C-14]levofloxacin was measured using OK cell monolayers grown on microporous membrane filters. Results. Transcellular transport from the basolateral to the apical side an d cellular accumulation of [C-14]PAH were inhibited by levofloxacin. Both t he initial uptake of [C-14]PAH from the basolateral side and the efflux to the apical side were inhibited by levofloxacin. The basolateral-to-apical t ranscellular transport of [C-14]levofloxacin was greater than that in the o pposite direction. [C-14]Levofloxacin efflux to the apical side was greater than that to the basolateral side. Unlabeled levofloxacin and grepafloxaci n inhibited the transcellular transport of [C-14]levofloxacin, accompanied by an increase of cellular accumulation. However, neither PAH nor an anion transport inhibitor 4-4 ' -diisothiocyanostilbene-2,2 ' -disulfonic acid (D IDS) affected the basolateral-to-apical transport of [C-14]levofloxacin nor its uptake from the basolateral side. Conclusions. These results indicated that levofloxacin inhibits PAH transpo rt across both the basolateral and apical membranes of OK cells, but are no t transported via the systems for PAH transport. The existence of a specifi c transport system for quinolones was indicated in OK cells.