Stereoselective Permeation of New Fluorinated Quinolone Derivatives across LLC-PK_1 Cell Monolayers
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概要
- 論文の詳細を見る
We examined the stereoselective membrane permeation of new fluorinated quinolone derivatives (NQs) across LLC-PK_1 cell monolayers, using levofloxacin (LVFX) and its R-(+) isomer. LVFX permeation was 1.6-fold greater in the basal-to-apical direction than that in the apical-to-basal direction, suggesting that LVFX permeated LLC-PK_1 cell monolayers in a secretory-oriented manner. In contrast to LVFX, the permeation of the R-(+) isomer was almost identical in both directions. LVFX permeation in the basal-to-apical direction was significantly reduced in the presence of guanidine, enoxacin, and L-arginine, whereas tetraethylammonium, D-arginine, D-and L-lysine had no effect on the basal-to-apical permeation of LVFX. Basal-to-apical permeation of the R-(+) isomer was not affected by these compounds. Cellular accumulation of LVFX was inversely increased when guanidine suppressed the appearance of LVFX in the apical medium in a concentration-dependent manner. These results imply that the inhibitory effect of guanidine on the basal-to-apical permeation of LVFX involves the permeation process across the apical membrane. Guanidine trans-stimulated the efflux of LVFX from LLC-PK_1 cells but did not affect cimetidine efflux. These results suggest that some NQs, like LVFX and its R-(+) isomer, are stereoselectively secreted across LLC-PK_1 cell monolayers and that an organic cation transport system, which favors guanidine as a typical substrate, may be involved in the secretory-oriented permeation of some NOs.
- 社団法人日本薬学会の論文
- 1999-07-15
著者
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齊藤 浩司
北海道医療大学薬学部
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齊藤 浩司
北海道医療大学薬学部:札幌腎と薬剤研究会
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齊藤 浩司
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaid
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SAITOH Hiroshi
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokka
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TAKADA Masahiko
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokka
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SASAYA Masafumi
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokka
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HATAKEYAMA Yuko
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokka
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佐藤 正基
School Of Pharmaceutical Sciences University Of Shizuoka(present Address):marusa Corporation
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Satoh M
Showa Pharmaceutical Univ. Tokyo Jpn
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Sato M
Otsuka Pharmaceutical Co. Ltd. Tokushima Jpn
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Hatakeyama Yuko
Department Of Cardio-angiology Kitasato University School Of Medicine
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Hatakeyama Yuko
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaid
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佐藤 真友美
Univ. Shizuoka Shizuoka Jpn
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Tanaka M
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaid
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Takada Masahiko
Department Of Morphological Brain Science Faculty Of Medicine Kyoto University
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Saitoh Hiroshi
Department Of Pediatrics Nihon University School Of Medicine
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Saitoh Hiroshi
Department Of Material Science And Technology Faculty Of Engineering Niigata University
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