Ohtomo T, Saito H, Inotsume N, Yasuhara M, Inui K I
Department of Hospital Pharmacy, School of Medicine, Tokyo Medical and Dental University, Japan.
J Pharmacol Exp Ther. 1996 Mar;276(3):1143-8.
The interactions of levofloxacin, a pyridonecarboxylic acid antibacterial drug, with the organic cation transport systems expressed in a pig kidney epithelial cell line, LLC-PK1, were examined. The transcellular transport of tetraethylammonium was remarkably inhibited by levofloxacin, accompanied by a marked increase in the cellular accumulation of tetraethylammonium in the LLC-PK1, monolayers grown on collagen-coated membrane filters. The results obtained by efflux and uptake of tetraethylammonium revealed that levofloxacin drastically inhibited the apical transport activity rather than the basolateral uptake of tetraethylammonium. Under conditions in which the apical efflux of tetraethylammonium was blocked by pretreatment with p-chloromercuribenzene sulfonate, levofloxacin showed a moderate inhibitory effect against the basolateral uptake of tetraethylammonium. Transepithelial flux of levofloxacin from the basolateral side to the apical side was much greater than the flux in the opposite direction. The flux of levofloxacin was influenced by the apical side pH, resulting in a decreased cellular accumulation by lowering pH. The basal-to-apical transport and cellular accumulation of levofloxacin were not inhibited by either tetraethylammonium or cimetidine. These results suggested that levofloxacin interacts with the apical H+/organic cation antiport system to a greater extent than with the basolateral system. However, transcellular transport of levofloxacin would be mediated by the transport systems which are distinct from the systems for tetraethylammonium in LLC-PK1 cells.
研究了吡啶酮羧酸类抗菌药物左氧氟沙星与猪肾上皮细胞系LLC-PK1中表达的有机阳离子转运系统的相互作用。在胶原包被的膜滤器上生长的LLC-PK1单层细胞中，左氧氟沙星显著抑制了四乙铵的跨细胞转运，同时伴随着四乙铵细胞内蓄积的明显增加。通过四乙铵的外排和摄取实验获得的结果表明，左氧氟沙星极大地抑制了四乙铵的顶端转运活性，而不是基底外侧摄取。在用对氯汞苯磺酸盐预处理阻断四乙铵顶端外排的条件下，左氧氟沙星对四乙铵的基底外侧摄取表现出中等程度的抑制作用。左氧氟沙星从基底外侧到顶端的跨上皮通量远大于相反方向的通量。左氧氟沙星的通量受顶端pH值影响，降低pH值会导致细胞内蓄积减少。四乙铵或西咪替丁均未抑制左氧氟沙星的基底到顶端转运及细胞内蓄积。这些结果表明，左氧氟沙星与顶端H⁺/有机阳离子反向转运系统的相互作用程度大于与基底外侧系统的相互作用。然而，LLC-PK1细胞中左氧氟沙星的跨细胞转运将由与四乙铵转运系统不同的转运系统介导。
