Development of the prediction system for tubular secretion of drugs in the human kidney
Project/Area Number |
18K06766
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47060:Clinical pharmacy-related
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Research Institution | Ritsumeikan University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | 薬物トランスポーター / 尿細管分泌 / 経細胞輸送 / 薬物相互作用 / 培養細胞 / 薬物動態学 / 腎排泄 / トランスポーター / in vitro評価 |
Outline of Final Research Achievements |
At present, it is difficult to accurately predict the degree of tubular secretion involved in renal excretion of drugs and the contribution of drug transporters involved in tubular secretion. In this study, we examined the effect of expression of transcription factors involved in the regulation of drug transporter expression on the expression of drug transporters in human kidney-derived HK-2 cells. It was demonstrated that HK-2 cells stably expressing HNF1α showed a increased expression of megalin, which is responsible for endocytosis of low molecular weight proteins and drugs. The nephrotoxicity of aminoglycoside antibiotics, substrates of megalin, is significantly enhanced in HK-2 cells stably expressing HNF1α.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、薬物の腎移行動態を評価しうる評価系の構築を目指したものであり、ヒト腎由来HK-2細胞においてHNF1αを発現させることにより、メガリンの発現が上昇することを明らかにした。メガリンを恒常的に発現するヒト由来培養腎上皮細胞は存在しないことから、HNF1α安定発現HK-2細胞は、メガリンの機能評価やアミノグリコシド系抗生物質の腎毒性評価が可能なin vitro実験系となりうることが示唆され、今後の新薬開発においても有用な評価系となることが期待される。
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Report
(5 results)
Research Products
(31 results)
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[Journal Article] Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation.2018
Author(s)
Ueshima S, Hira D, Kimura Y, Fujii R, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Ohno S, Horie M, Terada T, Katsura T.
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Journal Title
Br. J. Clin. Pharmacol.
Volume: -
Issue: 6
Pages: 1301-1312
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Population pharmacokinetics of edoxaban in Japanese patients with atrial fibrillation2021
Author(s)
Sayana Matsuda, Satoshi Ueshima, Daiki Hira, Rio Michihata, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Moritake Iguchi, Masaharu Akao, Satoshi Shizuta, Takeshi Makiyama, Yoshihisa Nakagawa, Minoru Horie, Tomohiro Terada, Toshiya Katsura
Organizer
第15回次世代を担う若手医療薬科学シンポジウム
Related Report
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[Presentation] Edoxaban blood concentrations vary considerably and correlate with anti-factor Xa activity in atrial fibrillation patients2020
Author(s)
Minoru Horie, Satoshi Ueshima, Daiki Hira, Toshiya Katsura, Tomohiro Terada, Kouichi Kato, Tomoya Ozawa, Hideki Itoh, Yohei Tabuchi, Miya Horie, Yoshihisa Nakagawa, Takeru Makiyama, Satoshi Shizuta, Asami Kashiwa, Takanori Aizawa, Takeshi Kimura, Moritake Iguchi, Masaharu Akao
Organizer
第84回日本循環器学会学術総会
Related Report
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[Presentation] Population pharmacokinetics and pharmacogenomics of rivaroxaban in Japanese patients with atrial fibrillation2020
Author(s)
Satoshi Ueshima, Daiki Hira, Kenji Kuwata, Karin Hirata, Yohei Tabuchi, Hideki Itoh, Tomoya Ozawa, Yoshihisa Nakagawa, Minoru Horie, Tomohiro Terada, Toshiya Katsura
Organizer
第30回日本医療薬学会年会
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[Presentation] Population pharmacokinetics and pharmacodynamics of apixaban in Japanese patients with atrial fibrillation2018
Author(s)
Satoshi Ueshima, Daiki Hira, Chiho Tomitsuka, Miki Nomura, Yuuma Kimura, Takuya Yamane, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Seiko Ohno, Minoru Horie, Tomohiro Terada, Toshiya Katsura
Organizer
18th World Congress of Basic and Clinical Pharmacology
Related Report
Int'l Joint Research
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