title: Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1.
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.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: I
authors.initials: I
authors.lastname: Yano
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: K I
authors.initials: KI
authors.lastname: Inui
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001692:Biological Transport; D003630:Daunorubicin / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D024841:Fluoroquinolones; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D018374:LLC-PK1 Cells; D064704:Levofloxacin; D015242:Ofloxacin / Q000493:pharmacokinetics*; D015363:Quinolones / Q000493:pharmacokinetics; D013552:Swine
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D064704:Levofloxacin; C076246:sitafloxacin; D015242:Ofloxacin; D003630:Daunorubicin