Involvement of Specific Transport System on Uptake of Lactone Form of SN-38 in Human Intestinal Epithelial Cell Line Caco-2
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- Ueno Yusuke
- Department of Clinical Pharmacy and Biopharmaceutics, Graduate School of Medicine, Mie University
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- Matsuda Hiroko
- Department of Clinical Pharmacy and Biopharmaceutics, Graduate School of Medicine, Mie University
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- Mizutani Hideki
- Department of Clinical Pharmacy and Biopharmaceutics, Graduate School of Medicine, Mie University College of Pharmacy, Kinjo Gakuin University
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- Iwamoto Takuya
- Department of Clinical Pharmacy and Biopharmaceutics, Graduate School of Medicine, Mie University
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- Okuda Masahiro
- Department of Clinical Pharmacy and Biopharmaceutics, Graduate School of Medicine, Mie University
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The aim of this study was to elucidate the characteristics of the transport of lactone and carboxylate forms of SN-38 (SN-38L and SN-38C, respectively), a metabolite of irinotecan hydrochloride (CPT-11), with the human intestinal epithelial cell line, Caco-2. We examined SN-38L and SN-38C uptake from the apical side into Caco-2, and the effects of various compounds on the uptake of SN-38L. SN-38L and SN-38C in the cells were determined by HPLC with a fluorescence detector. When either SN-38L (0.5 µM) or SN-38C (0.5 µM) was added extracellularly at 37°C, the accumulation of SN-38L into the cells was about 10-fold higher than that of SN-38C, suggesting a dominant role of the lactone form in the uptake of SN-38 into Caco-2. The accumulation of SN-38L in Caco-2 increased time-dependently up to 10 min at 37°C, whereas the accumulation markedly decreased at 4°C. The initial uptake rate of SN-38L approached saturation at high concentrations with Michaelis–Menten constant and ‘Hill coefficient,’ 2.84±1.00 μM and 2.13±1.14, respectively (mean±S.E.). The accumulation of SN-38L was markedly inhibited by baicalin, an active ingredient of a Chinese herbal medicine, Hange-Shashin-To, as well as CPT-11. The type of inhibition by baicalin was competitive. In contrast, concomitant sulfobromophthalein, taurocholate and estrone 3-sulfate significantly increased SN-38L uptake. These results suggest that apical uptake of SN-38 by Caco-2 is dominantly performed as a lactone form through a specific transporter, which is competitively inhibited by baicalin.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 35 (1), 54-58, 2012
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204632446848
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- NII論文ID
- 130001872342
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 024029643
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- 使用不可