Source:http://linkedlifedata.com/resource/pubmed/id/15618692
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2004-12-27
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| pubmed:abstractText |
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 [(14)C]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 beta-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.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:status |
PubMed-not-MEDLINE
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| pubmed:issn |
1347-4367
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
17
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
408-15
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| pubmed:year |
2002
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| pubmed:articleTitle |
New methods to evaluate intestinal drug absorption mediated by oligopeptide transporter from in vitro study using Caco-2 cells.
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| pubmed:affiliation |
Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan. shinji@pharm.setsunan.ac.jp
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| pubmed:publicationType |
Journal Article
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