Transport of levofloxacin in the OK kidney epithelial cell line : Interaction with p-aminohippurate transport

• Published in: Pharmaceutical research Vol. 18; no. 5; pp. 573 - 578
• Main Authors: MATSUO, Yumiko, YANO, Ikuko, HABU, Yasushi, KATSURA, Toshiya, HASHIMOTO, Yukiya, INUI, Ken-Ichi
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.05.2001; Springer Nature B.V
• Subjects: Acids; Animals; Anti-Infective Agents - metabolism; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Biological Transport, Active; Cell Line; Cell physiology; Cells; Drugs; Epithelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Glucose; Kidney - metabolism; Kinetics; Levofloxacin; Medical sciences; Membrane and intracellular transports; Membranes; Molecular and cellular biology; Ofloxacin - metabolism; p-Aminohippuric Acid - metabolism; Pharmaceuticals; Pharmacology. Drug treatments; Japan; Levofloxacin; Organic anion; Fluoroquinolone derivatives; Urinary system; Hippuric acid; Membrane transport; Biological transport; Established cell line; Antibacterial agent; In vitro; Quinolone derivatives; Kidney
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1011012822437

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