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Inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h between alpha-tocopherol and ezetimibe

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Title: Inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h between alpha-tocopherol and ezetimibe
Authors: Nashimoto, Shunsuke Browse this author
Sato, Yuki Browse this author →KAKEN DB
Takekuma, Yoh Browse this author →KAKEN DB
Sugawara, Mitsuru Browse this author →KAKEN DB
Keywords: alpha-tocopherol
Issue Date: May-2017
Publisher: John Wiley & Sons
Journal Title: Biopharmaceutics & drug disposition
Volume: 38
Issue: 4
Start Page: 280
End Page: 289
Publisher DOI: 10.1002/bdd.2059
PMID: 28027412
Abstract: Tocopherol is used not only as an ethical drug but also as a supplement. In 2008, it was reported that alpha-tocopherol is partly transported via an intestinal cholesterol transporter, Niemann-Pick C1-Like 1 (NPC1L1). Ezetimibe, a selective inhibitor of NPC1L1, is administered for a long time to inhibit cholesterol absorption and there is a possibility that the absorption of alpha-tocopherol is also inhibited by ezetimibe. This study investigated the influence of ezetimibe on the absorption of alpha-tocopherol with single administration and long-term administration. An approach to avoid its undesirable consequence was also examined. alpha-Tocopherol (10 mg/kg) and ezetimibe (0.1 mg/kg) were administered to rats, and the plasma concentration profiles of alpha-tocopherol and tissue concentrations were investigated. The plasma concentration of alpha-tocopherol was decreased by the combination use of ezetimibe in the case of concurrent single administration. On the other hand, inhibition of the absorption of alpha-tocopherol was prevented by an administration interval of 4 h. In a group of rats administered for 2 months with a 4 h interval, not only the plasma concentration but also the liver concentration was increased compared with those in a group with concurrent combination intake of alpha-tocopherol and ezetimibe. The absorption of alpha-tocopherol was inhibited by ezetimibe. The inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h, although ezetimibe is a medicine of enterohepatic circulation. Attention should be paid to the use of ezetimibe and components of NPC1L1 substrates such as alpha-tocopherol. Copyright (C) 2016 John Wiley & Sons, Ltd.
Rights: This is the peer reviewed version of the following article: Biopharmaceutics & drug disposition 2017 May;38(4):280-289, which has been published in final form at DOI:10.1002/bdd.2059. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
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: 佐藤 夕紀

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