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  • Title: Transport of quinolone antibacterial drugs in a kidney epithelial cell line, LLC-PK1.
    Author: Matsuo Y, Yano I, Ito T, Hashimoto Y, Inui K.
    Journal: J Pharmacol Exp Ther; 1998 Nov; 287(2):672-8. PubMed ID: 9808695.
    Abstract:
    The transport of quinolone antibacterial drugs by LLC-PK1 monolayers was examined to characterize the renal tubular secretion of these drugs. The transcellular transport of levofloxacin and grepafloxacin from the basolateral to apical side was larger than the transport in the opposite direction. The basal-to-apical transcellular transport and uptake from the basolateral side of levofloxacin showed concentration dependent saturation with an apparent Michaelis constant (Km) of 0.6 and 13 mM, respectively. Various quinolones (1 mM) inhibited the transcellular transport of levofloxacin, and this inhibition was accompanied by a marked increase of cellular accumulation. These results indicated that quinolones interacted more strongly with the transport system on the apical than the basolateral membrane. Neither tetraethylammonium nor cyclosporin A affected the basal-to-apical transcellular transport and accumulation of levofloxacin. The basal-to-apical transcellular transport of levofloxacin was not influenced by either lowering the pH of the apical side or pretreatment of apical membrane with p-chloromercuribenzene sulfonate. These findings indicate that quinolones are specifically transported from the basolateral to apical side by LLC-PK1 monolayers and have higher affinity for the transport system in the apical membrane, a system distinct from H+/organic cation antiport system.
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