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Identification of the entrance for vitamin in the intestine

Towards appropriate pharmacotherapy considering alteration of vitamin absorption

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University Hospital
2015/03/13

© 2015 Yoshihide Yamanashi and Kentaro Konishi

© 2015 Yoshihide Yamanashi and Kentaro Konishi

Vitamin K is an essential nutrient that activates blood coagulation. Recently, vitamin K has attracted considerable attention because of its physiological functions which include protective and/or therapeutic effects against osteoporosis and atherosclerosis. Since we cannot synthesize vitamin K in our body, it is necessary to ingest this nutrient as part of our diet. However, the molecular mechanism of intestinal vitamin K absorption remained unknown.

A research group including Associate Professor Tappei Takada, Assistant Professor Yoshihide Yamanashi, former graduate student Kentaro Konishi and Professor Hiroshi Suzuki at the Department of Pharmacy, the University of Tokyo Hospital, demonstrated for the first time that NPC1L1, a cholesterol transporter protein, has an important role in intestinal vitamin K absorption. Ezetimibe, an NPC1L1 inhibitor clinically used for dyslipidemia, has been reported to enhance the pharmacological effect of warfarin, an anticoagulant drug. However, the mechanism of this drug-drug interaction was not clear. Based on the finding that vitamin K is mainly absorbed by the NPC1L1-mediated pathway, the research group found via pharmacological studies that the ezetimibe-warfarin interaction can be accounted for by the ezetimibe-related vitamin K malabsorption.

These findings will contribute to better understanding of regulatory mechanisms of intestinal vitamin K absorption and whole-body vitamin levels, and, in addition, promote effective pharmacotherapy and appropriate dose settings considering the alteration of vitamin absorption.

Press release (Japanese)

Paper

Tappei Takada, Yoshihide Yamanashi, Kentaro Konishi, Tekehito Yamamoto, Yu Toyoda, Yusuke Masuo, Hideaki Yamamoto, Hiroshi Suzuki, "NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy", Science Translational Medicine Vol. 7, issue 275, (2015), doi: 10.1126/scitranslmed.3010329.
Article link (Publication)

Links

The University of Tokyo Hospital

Department of Pharmacy, The University of Tokyo Hospital

Graduate School of Pharmaceutical Sciences

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