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ID 118209
Title Alternative
新規総リン酸トランスポーター阻害剤EOS789のリン代謝に対する効果 : 既存リン吸着剤との比較
The physiological effects of EOS789
Author
Tanifuji, Kazuya Tokushima University
Koike, Megumi Tokushima University
Uga, Minori Tokushima University
Komiya, Aoi Tokushima University
Miura, Mizuki Tokushima University
Higashi, Ayami Tokushima University
Ishizuka, Noriko University of Shizuoka
Hayashi, Hisayoshi University of Shizuoka
Ichida, Yasuhiro Chugai Pharmaceutical Co., Ltd.
Ohtomo, Shuichi Chugai Pharmaceutical Co., Ltd.
Horiba, Naoshi Chugai Pharmaceutical Co., Ltd.
Keywords
hyperphosphatemia
CKD
intestine
phosphate transporter
Content Type
Thesis or Dissertation
Description
Background: Inorganic phosphate (Pi) binders are the only pharmacologic treatment approved for hyperphosphatemia. However, Pi binders induce the expression of intestinal Pi transporters and have limited effects on the inhibition of Pi transport. EOS789, a novel pan-Pi transporter inhibitor, reportedly has potent efficacy in treating hyperphosphatemia. We investigated the properties of EOS789 with comparison to a conventional Pi binder. Methods: Protein and mRNA expression levels of Pi transporters were measured in intestinal and kidney tissues from male Wistar rats fed diets supplemented with EOS789 or lanthanum carbonate (LC). 32Pi permeability was measured in intestinal tissues from normal rats using a chamber. Results: Increased protein levels of NaPi-2b, an intestinal Pi transporter, and luminal Pi removal were observed in rats treated with LC but not in rats treated with EOS789. EOS789 but not LC suppressed intestinal protein levels of the Pi transporter Pit-1 and sodium / hydrogen exchanger isoform 3. 32Pi flux experiments using small intestine tissues from rats demonstrated that EOS789 may affect transcellular Pi transport in addition to paracellular Pi transport. Conclusion: EOS789 has differing regulatory effects on Pi metabolism compared to LC. The properties of EOS789 may compensate for the limitations of LC therapy. The combined or selective use of EOS789 and conventional Pi binders may allow tighter control of hyperphosphatemia.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
Publisher
Tokushima University Faculty of Medicine
Volume
70
Issue
1-2
Start Page
260
End Page
270
Sort Key
260
Published Date
2023-02
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Kazuya Tanifujiの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3733号
Diploma Number
甲栄第298号
Granted Date
2023-03-24
Degree Name
Doctor of Nutritional Science
Grantor
Tokushima University
departments
Medical Sciences