Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1.

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Ito T, Yano I, Tanaka K, Inui KI

Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1.

J Pharmacol Exp Ther. 1997 Aug;282(2):955-60.

PubMed ID

9262363 [ View in PubMed

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Abstract

The purpose of this study was to characterize the transport mechanisms involved in the renal tubular secretion of quinolones. The contribution of P-glycoprotein to the transport of quinolones was elucidated using a kidney epithelial cell line, LLC-PK1, and its transfectant derivative cell line, LLC-GA5-COL150, which expresses human P-glycoprotein on the apical membrane. The transcellular transport of levofloxacin, a quinolone antibacterial drug, from the basolateral to apical side was increased in LLC-GA5-COL150 compared with that in LLC-PK1 monolayers. The apparent Michaelis constant and maximum velocity values for the saturable transcellular transport of levofloxacin from the basolateral to apical side in LLC-GA5-COL150 monolayers were 3.0 mM and 45 nmol/mg protein per 15 min, respectively. The increased basolateral-to-apical transport in LLC-GA5-COL150 monolayers was completely inhibited by cyclosporin A and quinidine to the level observed in LLC-PK1 monolayers. In addition, 3 mM levofloxacin inhibited the basolateral-to-apical transport of daunorubicin in LLC-GA5-COL150 monolayers. The basolateral-to-apical transport of another quinolone antibacterial drug, DU-6859a, in LLC-GA5-COL150 monolayers greatly exceeded than that in LLC-PK1 monolayers, and was inhibited by levofloxacin. These findings suggest that quinolone antibacterial drugs are transported by P-glycoprotein, and that P-glycoprotein may contribute at least in part to the renal tubular secretion of quinolones.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Cimetidine	P-glycoprotein 1	Protein	Humans	Unknown	Substrate Inducer	Details
Levofloxacin	P-glycoprotein 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Quinidine	P-glycoprotein 1	Protein	Humans	Unknown	Substrate Inhibitor	Details