Interactions of Fluoroquinolone Antibacterials, DX-619 and Levofloxacin, with Creatinine Transport by Renal Organic Cation Transporter hOCT2

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  • OKUDA Masahiro
    Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
  • KIMURA Naoko
    Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
  • INUI Ken-ichi
    Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

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  Interactions of DX-619, a novel fluoroquinolone antibacterial, and levofloxacin (LVFX) with the human renal organic cation transporter hOCT2 were studied. The intracellular accumulation of [14C]creatinine in stable transfectants of HEK293 cells expressing hOCT2 (hOCT2-HEK293) as well as vector-transfected HEK293 cells (VEC-HEK293) was evaluated in the presence of DX-619 and LVFX at various concentrations. When added extracellularly, both DX-619 and LVFX inhibited the uptake of [14C]creatinine (5 μM) by hOCT2-HEK293 cells in a dose-dependent manner. Unlike in hOCT2-HEK293 cells, the uptake in VEC-HEK293 cells was not inhibited by either fluoroquinolone suggesting that hOCT2 was specifically involved in the inhibition. The apparent IC50 value for the inhibition of [14C]creatinine uptake in hOCT2-HEK293 cells was 1.29±0.23 μM for DX-619 and 127±27 μM for LVFX, indicating DX-619 to be ~100-fold more potent than LVFX at inhibiting the transport of [14C]creatinine by hOCT2. A Dixon plot revealed that the inhibition by DX-619 of the hOCT2-mediated transport of [14C]creatinine was competitive. Fluoroquinolone antibacterials have the ability to inhibit the transport of creatinine by hOCT2, with DX-619 being much more effective than LVFX.<br>

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