TRANSPORT OF QUINOLONE ANTIBACTERIAL DRUGS IN A KIDNEY EPITHELIAL-CELL LINE, LLC-PK1

The transport of quinolone antibacterial drugs by LLC-PK1 monolayers w as examined to characterize the renal tubular secretion of these drugs . The transcellular transport of levofloxacin and grepafloxacin from t he basolateral to apical side was larger than the transport in the opp osite direction. The basal-to-apical transcellular transport and uptak e from the basolateral side of levofloxacin showed concentration depen dent saturation with an apparent Michaelis constant (K-m) of 0.6 and 1 3 mM, respectively. Various quinolones (1 mM) inhibited the transcellu lar transport of levofloxacin, and this inhibition was accompanied by a marked increase of cellular accumulation. These results indicated th at quinolones interacted more strongly with the transport system on th e apical than the basolateral membrane. Neither tetraethylammonium nor cyclosporin A affected the basal-to-apical transcellular transport an d accumulation of levofloxacin. The basal-to-apical transcellular tran sport of levofloxacin was not influenced by either lowering the pH of the apical side or pretreatment of apical membrane with p-chloromercur ibenzene sulfonate. These findings indicate that quinolones are specif ically transported from the basolateral to apical side by LLC-PK1 mono layers and have higher affinity for the transport system in the apical membrane, a system distinct from H+/organic cation antiport system.