The Effects of Jabara Juice on the Intestinal Permeation of Fexofenadine
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- Han Hongye
- Graduate School of Pharmaceutical Sciences, Keio University
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- Akiyoshi Takeshi
- Graduate School of Pharmaceutical Sciences, Keio University Department of Clinical Pharmacokinetics, School of Medicine, Keio University
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- Morita Tokio
- Graduate School of Pharmaceutical Sciences, Keio University
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- Tsuchitani Toshiaki
- Graduate School of Pharmaceutical Sciences, Keio University
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- Nabeta Momoko
- Graduate School of Pharmaceutical Sciences, Keio University
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- Yajima Kodai
- Graduate School of Pharmaceutical Sciences, Keio University
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- Imaoka Ayuko
- Graduate School of Pharmaceutical Sciences, Keio University
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- Ohtani Hisakazu
- Graduate School of Pharmaceutical Sciences, Keio University Department of Clinical Pharmacokinetics, School of Medicine, Keio University Department of Pharmacy, Keio University Hospital
抄録
<p>Jabara juice and its component narirutin inhibit the activity of organic anion-transporting polypeptides (OATPs) 1A2 and OATP2B1, which are considered to play significant roles in the intestinal absorption of fexofenadine. In this study, we investigated the effects of jabara juice on the intestinal absorption of fexofenadine in mice and the inhibitory effects of jabara juice and narirutin on the permeation of fexofenadine using Caco-2 cell monolayers and LLC-GA5-COL300 cell monolayers. In the in vivo study, the area under the plasma concentration–time curve (AUC) of fexofenadine in mice was increased 1.8-fold by jabara juice. In the permeation study, 5% jabara juice significantly decreased the efflux ratio (ER) of fexofenadine for Caco-2 monolayers. Furthermore, the ERs of fexofenadine and digoxin, which is a typical substrate of P-glycoprotein (P-gp), for LLC-GA5-COL300 cell monolayers were decreased in a concentration-dependent manner by jabara juice extract, suggesting that jabara juice may increase the intestinal absorption of fexofenadine by inhibiting P-gp, rather than by narirutin inhibiting OATPs. The present study showed that jabara juice increases the intestinal absorption of fexofenadine both in vivo and in vitro. The intestinal absorption of fexofenadine may be altered by the co-administration of jabara juice in the clinical setting.</p>
収録刊行物
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- Ｂｉｏｌｏｇｉｃａｌ ＆ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｂｕｌｌｅｔｉｎ
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Ｂｉｏｌｏｇｉｃａｌ ＆ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｂｕｌｌｅｔｉｎ 46 (12), 1745-1752, 2023-12-01
公益社団法人 日本薬学会