HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >

In vitro and in vivo evaluation of organic anion-transporting polypeptide 2B1-mediated pharmacokinetic interactions by apple polyphenols

Files in This Item:
Manuscript_Takahashi et al.pdf2.7 MBPDFView/Open
Please use this identifier to cite or link to this item:

Title: In vitro and in vivo evaluation of organic anion-transporting polypeptide 2B1-mediated pharmacokinetic interactions by apple polyphenols
Authors: Takahashi, Yuka Browse this author
Narumi, Katsuya Browse this author →KAKEN DB
Nadai, Takanobu Browse this author
Ueda, Hinata Browse this author
Yamamura, Taiki Browse this author
Furugen, Ayako Browse this author →KAKEN DB
Kobayashi, Masaki Browse this author →KAKEN DB
Keywords: phloretin
Organic Anion-transporting Polypeptide 2B1
Issue Date: 24-Aug-2021
Publisher: Taylor & Francis
Journal Title: Xenobiotica
Volume: 51
Issue: 11
Start Page: 1318
End Page: 1325
Publisher DOI: 10.1080/00498254.2021.1969480
Abstract: Organic anion-transporting polypeptide (OATP) 2B1 plays a critical role in the intestinal absorption of substrate drugs. Apple juice reportedly interacts with OATP2B1 substrate drugs. The purpose of this study was to investigate the effect of two apple polyphenols, phloretin and phloridzin, on OATP2B1-mediated substrate transport in vitro and to evaluate the effect of phloretin on rosuvastatin pharmacokinetics in rats. In vitro studies revealed that both polyphenols inhibited OATP2B1-mediated uptake of estrone-3-sulfate. Despite preincubation with phloretin and subsequent washing, the inhibitory effect was retained. Phloretin markedly decreased OATP2B1-mediated rosuvastatin uptake, with an IC50 value of 3.6 mu M. On coadministering rosuvastatin and phloretin in rats, the plasma concentration of rosuvastatin 10 min after oral administration was significantly lower than that in the vehicle group. The area under the plasma concentration-time curve of rosuvastatin was not significant, showing a tendency to decrease in the phloretin group when compared with the vehicle group. The in-situ rat intestinal loop study revealed the inhibitory effect of phloretin on rosuvastatin absorption. Phloretin has potent and long-lasting inhibitory effects on OATP2B1 in vitro. Phloretin may inhibit OATP2B1-mediated intestinal absorption of rosuvastatin; however, it failed to significantly impact the systemic exposure of rosuvastatin in rats.
Rights: This is an Accepted Manuscript of an article published by Taylor & Francis in Xenobiotica on 24 Aug. 2021, available online:
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 鳴海 克哉

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 - Hokkaido University