TRANSPORT OF LEVOFLOXACIN IN A KIDNEY EPITHELIAL-CELL LINE, LLC-PK1 -INTERACTION WITH ORGANIC CATION TRANSPORTERS IN APICAL AND BASOLATERAL MEMBRANES

The interactions of levofloxacin, a pyridonecarboxylic acid antibacter ial drug, with the organic cation transport systems expressed in a pig kidney epithelial cell line, LLC-PK1, were examined. The transcellula r transport of tetraethylammonium was remarkably inhibited by levoflox acin, accompanied by a marked increase in the cellular accumulation of tetraethylammonium in the LLC-PK1 monolayers grown on collagen-coated membrane filters. The results obtained by efflux and uptake of tetrae thylammonium revealed that levofloxacin drastically inhibited the apic al transport activity rather than the basolateral uptake of tetraethyl ammonium. Under conditions in which the apical efflux of tetraethylamm onium was blocked by pretreatment with p-chloromercuribenzene sulfonat e, levofloxacin showed a moderate inhibitory effect against the basola teral uptake of tetraethylammonium, Transepithelial flux of levofloxac in from the basolateral side to the apical side was much greater than the flux in the opposite direction. The flux of levofloxacin was influ enced by the apical side pH, resulting in a decreased cellular accumul ation by lowering pH. The basal-to-apical transport and cellular accum ulation of levofloxacin were not inhibited by either tetraethylammoniu m or cimetidine. These results suggested that levofloxacin interacts w ith the apical H+/organic cation antiport system to a greater extent t han with the basolateral system. However, transcellular transport of l evofloxacin would be mediated by the transport systems which are disti nct from the systems for tetraethylammonium in LLC-PK1 cells.