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In vitro and in vivo evaluation of organic anion-transporting polypeptide 2B1-mediated pharmacokinetic interactions by apple polyphenols
| 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 | | phloridzin | | rosuvastatin | | 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: http://www.tandfonline.com/10.1080/00498254.2021.1969480. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/87010 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 鳴海 克哉
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