New Methods to Evaluate Intestinal Drug Absorption Mediated by Oligopeptide Transporter from In vitro Study using Caco-2 Cells
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- YAMASHITA Shinji
- Faculty of Pharmaceutical Sciences, Setsunan University
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- HATTORI Emiko
- Faculty of Pharmaceutical Sciences, Setsunan University
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- SHIMADA Aiko
- Faculty of Pharmaceutical Sciences, Setsunan University
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- ENDOH Yoriko
- Faculty of Pharmaceutical Sciences, Setsunan University
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- YAMAZAKI Yukako
- Faculty of Pharmaceutical Sciences, Setsunan University
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- KATAOKA Makoto
- Faculty of Pharmaceutical Sciences, Setsunan University
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- SAKANE Toshiyasu
- Faculty of Pharmaceutical Sciences, Setsunan University
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- SEZAKI Hitoshi
- Faculty of Pharmaceutical Sciences, Setsunan University
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The aim of the present work is to develop a convenient and rapid screening system in vitro for intestinal drug absorption mediated by oligopeptide transporter (PepT1). In this study, (1) Transports of cephalexin (CEX) and L-phenylalanine (L-Phe) across Caco-2 monolayers were measured and compared with those of passively transported drugs, (2) Inhibitory effects of various drugs on the transport of [14C]glycylsarcosine (Gly-Sar) across Caco-2 monolayers were measured and correlated with their in vivo permeability to rat small intestine, (3) Intracellular pH-change induced by co-transport of drugs with proton into Caco-2 cells was monitored by using Fluorometric Imaging Plate Reader (FLIPR, Molecular Devices Corp.). Concentration-dependent transport was observed in Caco-2 monolayers for CEX and L-Phe, although their permeability was relatively low compared to those of passively transported drugs. Inhibitory effects of various drugs including β-lactam antibiotics and angiotensin converting enzyme-inhibitors on the transport of Gly-Sar correlated well with their in vivo permeability to rat small intestine. It was demonstrated that CEX, but not cefazolin, induced gradual decrease in the intracellular pH of Caco-2 cells. The degree of intracellular pH-change caused by various drugs showed a sigmoidal or saturable relationship with their permeability to rat small intestine. These in vitro approaches with Caco-2 cells should be useful to evaluate in vivo intestinal permeability of drugs mediated by PepT1, suggesting a possibility of high throughput screening of drug absorption.<br>
収録刊行物
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 17 (5), 408-415, 2002
日本薬物動態学会
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詳細情報 詳細情報について
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- CRID
- 1390282680157920512
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- NII論文ID
- 10010130449
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- NII書誌ID
- AA1162652X
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- ISSN
- 18800920
- 13474367
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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
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- 抄録ライセンスフラグ
- 使用不可