2001年8月
Transport characteristics of ebastine and its metabolites across human intestinal epithelial Caco-2 cell monolayers
BIOLOGICAL & PHARMACEUTICAL BULLETIN
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- 巻
- 24
- 号
- 8
- 開始ページ
- 930
- 終了ページ
- 934
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1248/bpb.24.930
- 出版者・発行元
- PHARMACEUTICAL SOC JAPAN
The transport characteristics of a selective peripheral H-1 receptor antagonist, ebastine, a substrate for cytochrome P450 3A4, and its three major metabolites, i.e., the hydroxy metabolite of ebastine (M-OH), the pharmacologically active metabolite carebastine (Car), and the desbutyrophenone metabolite (des-BP), were studied in cultured human intestinal Caco-2 cells expressing a drug efflux pump, P-glycoprotein (P-gp), on the apical membrane. The polarized transport of [H-3]cyclosporin A (CyA), mediated by P-gp in the basolateral to apical direction across the Caco-2 cell monolayers, was affected by the presence of ebastine in a concentration-dependent manner and significant inhibition was observed at high concentrations (>50 muM). M-OH (300 muM) also significantly inhibited whereas Car and des-BP did not. Although no marked polarized transport of [C-14]ebastine in a secretory direction was observed in the Caco-2 systems, the flux in the basolateral to apical direction was slightly higher than that in the opposite direction at concentrations less than 30 muM. [C-14]Ebastine (2 muM) uptake from the apical side was significantly increased in the presence of an excess of cold CyA, suggesting that the efflux process mediated by P-gp may be involved in the ebastine uptake by Caco-2 cells. Collectively, these results indicate that ebastine (and presumably M-OH) is transported via P-gp in Caco-2 cells, however, the affinity for P-gp is very low. It is unlikely that the secretory transport of ebastine mediated by P-gp will dramatically affect overall intestinal absorption in vivo because efficient passive diffusion of this drug should occur due to its high lipophilicity. However, it may be advantageous for its efficient first-pass metabolism.
- リンク情報
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- DOI
- https://doi.org/10.1248/bpb.24.930
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902111033491512
- CiNii Articles
- http://ci.nii.ac.jp/naid/110003638591
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/11510488
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000170110700015&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1248/bpb.24.930
- ISSN : 0918-6158
- J-Global ID : 200902111033491512
- CiNii Articles ID : 110003638591
- PubMed ID : 11510488
- Web of Science ID : WOS:000170110700015