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Transport of Levofloxacin in the OK Kidney Epithelial Cell Line: Interaction with p-Aminohippurate Transport

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Abstract

Purpose. To evaluate the mechanism of renal transport of quinolone antibacterial drugs, we examined the interaction of levofloxacin with p–aminohippurate (PAH) transport systems and the transport of levofloxacin in renal epithelial cells.

Methods. Transport of [14C]PAH or [14C]levofloxacin was measured using OK cell monolayers grown on microporous membrane filters.

Results. Transcellular transport from the basolateral to the apical side and cellular accumulation of [14C]PAH were inhibited by levofloxacin. Both the initial uptake of [14C]PAH from the basolateral side and the efflux to the apical side were inhibited by levofloxacin. The basolateral–to–apical transcellular transport of [14C]levofloxacin was greater than that in the opposite direction. [14C]Levofloxacin efflux to the apical side was greater than that to the basolateral side. Unlabeled levofloxacin and grepafloxacin inhibited the transcellular transport of [14C]levofloxacin, accompanied by an increase of cellular accumulation. However, neither PAH nor an anion transport inhibitor 4–4′–diisothiocyanostilbene–2,2′–disulfonic acid (DIDS) affected the basolateral–to–apical transport of [14C]levofloxacin nor its uptake from the basolateral side.

Conclusions. These results indicated that levofloxacin inhibits PAH transport across both the basolateral and apical membranes of OK cells, but are not transported via the systems for PAH transport. The existence of a specific transport system for quinolones was indicated in OK cells.

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  1. Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo–ku, Kyoto, 606–8507, Japan

    Yumiko Matsuo, Ikuko Yano, Yasushi Habu, Toshiya Katsura, Yukiya Hashimoto & Ken–ichi Inui

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  1. Yumiko Matsuo
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  2. Ikuko Yano
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  3. Yasushi Habu
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  4. Toshiya Katsura
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  5. Yukiya Hashimoto
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  6. Ken–ichi Inui
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Matsuo, Y., Yano, I., Habu, Y. et al. Transport of Levofloxacin in the OK Kidney Epithelial Cell Line: Interaction with p-Aminohippurate Transport. Pharm Res 18, 573–578 (2001). https://doi.org/10.1023/A:1011012822437

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  • DOI: https://doi.org/10.1023/A:1011012822437

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