Pharmacokinetic Analysis of Transcellular Transport of Levofloxacin across LLC-PK_1 and Caco-2 Cell Monolayers(Biopharmacy)
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概要
- 論文の詳細を見る
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.
- 公益社団法人日本薬学会の論文
- 2007-11-01
著者
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HASHIMOTO Yukiya
Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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Hashimoto Y
Graduate School Of Pharmaceutical Sciences Kyushu University
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TAHARA Katsutoshi
Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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Hashimoto Yuichi
Institute Of Molecular & Cellular Biosciences University Of Tokyo
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Harada Yuichi
Center For Influenza Virus Research National Institute Of Infectious Diseases
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Ishida Kazuya
Graduate School Of Medicine And Pharmaceutical Sciences Univ. Of Toyama
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Hashimoto Yukiya
Graduate School Of Medicine And Pharmaceutical Sciences Univ. Of Toyama
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TAKAAI Mari
Graduate School of Pharmaceutical Sciences, University of Toyama
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SUZUKI Hisaki
Graduate School of Pharmaceutical Sciences, University of Toyama
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Suzuki Hisaki
Graduate School Of Pharmaceutical Sciences University Of Toyama
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Hashimoto Y
Institute Of Molecular & Cellular Biosciences The University Of Tokyo
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Tahara Katsutoshi
Graduate School Of Medicine And Pharmaceutical Sciences University Of Toyama
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Hashimoto Yuichi
Institute of Molecular & Cellular Biosciences, The University of Tokyo
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Takaai Mari
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
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