Pharmacokinetic analysis of transcellular transport of levofloxacin across LLC-PK1 and Caco-2 cell monolayers.
Pharmacokinetic analysis of transcellular transport of levofloxacin across LLC-PK1 and Caco-2 cell monolayers.
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左氧氟沙星跨 LLC-PK1 和 Caco-2 细胞单层的跨细胞转运的药代动力学分析。
DOI：
10.1248/bpb.30.2167
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发表时间：
2007
影响因子：
2
通讯作者：
Y. Hashimoto
中科院分区：
文献类型：
--
作者：
M. Takaai;Hisaki Suzuki;Kazuya Ishida;K. Tahara;Y. Hashimoto
为了表征负责左氧氟沙星的肾脏排泄和肠道吸收的膜转运，我们对LLC-PK（1）和Caco-2细胞单层的跨细胞转运进行了药代动力学分析。左氧氟沙星在LLC-PK（1）细胞中的跨细胞转运在基底外侧至顶端方向上大于相反方向。药代动力学分析表明，在LLC-PK（1）细胞中，基底外侧摄取是左氧氟沙星跨细胞转运的方向决定步骤。在LLC-PK（1）细胞中，左氧氟沙星的顶端外排清除率在培养基pH 6时比pH 8时增加，这表明左氧氟沙星的膜转运特征与原型有机阳离子四乙基铵的膜转运特征明显相似。另一方面，左氧氟沙星在Caco-2细胞中的跨细胞转运仅在基底侧向至顶端方向上比在相反方向上略大。左氧氟沙星在Caco-2细胞中的顶端流出清除率大于基底外侧流出清除率，顶端流入清除率大于任何其他膜转运清除率。此外，尼古丁和丙咪嗪显著抑制左氧氟沙星和奎尼丁在Caco-2细胞的顶端摄取。结果表明，一些转运蛋白不仅负责流出，而且还负责左氧氟沙星在Caco-2细胞顶膜的内流。
To characterize the membrane transport responsible for the renal excretion and intestinal absorption of levofloxacin, we performed pharmacokinetic analysis of transcellular transport across LLC-PK(1) and Caco-2 cell monolayers. Transcellular transport of levofloxacin in LLC-PK(1) cells was greater in the basolateral-to-apical direction than in the opposite direction. Pharmacokinetic analysis indicated that basolateral uptake was the direction-determining step for the transcellular transport of levofloxacin in LLC-PK(1) cells. The apical efflux clearance of levofloxacin in LLC-PK(1) cells was increased at the medium pH 6 as compared with at pH 8, suggesting that membrane transport characteristics of levofloxacin are apparently similar to those of a prototypical organic cation, tetraethylammonium. On the other hand, transcellular transport of levofloxacin in Caco-2 cells was only slightly greater in the basolateral-to-apical direction than in the opposite direction. The apical efflux clearance of levofloxacin in Caco-2 cells was greater than basolateral efflux clearance, and apical influx clearance was greater than any other membrane transport clearance. In addition, the apical uptake of levofloxacin as well as quinidine in Caco-2 cells was inhibited significantly by nicotine and imipramine. The findings indicated that some transporters are responsible not only for the efflux but also for the influx of levofloxacin at the apical membrane of Caco-2 cells.
影响因子：
5.8
作者：
Tanihara, Yuko;Masuda, Satohiro;Inui, Ken-ichi
通讯作者：
Inui, Ken-ichi