Study on transporter activities and its interactions between organ systems in chronic kidney disease by positron emission tomography

• Project/Area Number: 17K15535
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kaneko Kenichi 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (30776513)
• Research Collaborator: Watanabe Yasuyoshi ; Cui Yilong ; Hosoya Takamitsu ; Doi Hisashi ; Niwa Takashi ; Uetake Yuta ; Suezaki Yoshie ; Nakaoka Takayoshi ; Irie Satsuki ; Maruyama Toru ; Watanabe Hiroshi
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: PET / 薬物トランスポーター / 慢性腎臓病 / 薬物動態学的解析 / 医療系薬学 / 医療薬剤学

Outline of Final Research Achievements

We demonstrated that the concentration of [18F]Pitavastatin in the liver, kidney and bile of model rats with chronic kidney disease (CKD) was quantitatively measured by PET imaging. We show that the excretion of [18F]Pitavastatin from kidney decreased in the model rats with CKD compared with the sham rats although there was almost no difference between the blood concentration of [18F]Pitavastatin in the model rats with CKD and that in the sham rats. These results indicate that PET can evaluate the change of organ clearance that it is not easy to analyze from the only measurement of drug concentration in blood. Therefore, this study provides important information on the quantitative and serial measurement of drug concentration in organs.

Academic Significance and Societal Importance of the Research Achievements

臓器中の薬物濃度を経時的に定量することで、血中濃度の変化を伴わない臓器クリアランス低下を評価できたこと、更なる検討が必要ではあるが、慢性腎臓病時には、血中および臓器中薬物濃度だけではなく、薬物の血清タンパク結合率および血中の尿毒症物質濃度も合わせて評価する必要があることを示すことができたという点で、臨床応用に向けた基盤構築をする上で非常に有用であったと考えられる。

Research Products

• [Presentation] A clinical quantitative evaluation of hepatobiliary transport of [11C]Dehydropravastatin in humans using positron emission tomography (2018)
  • Author(s): Ken-ichi Kaneko, Masaaki Tanaka, Akira Ishii, Takayoshi Nakaoka, Satsuki Irie, Yasuhiro Wada, Takeshi Miyake, Kota Toshimoto, Kazuya Maeda, Yilong Cui, Masaru Enomoto, Etsushi Kawamura, Norifumi Kawada, Joji Kawabe, Hiroyuki Kusuhara, Yuichi Sugiyama, and Yasuyoshi Watanabe.
  • Organizer: 2018 International Meeting on 22nd MDO and 33rd JSSX
  • Int'l Joint Research
• [Presentation] Clinical evaluation of [18F]Pitavastatin for quantitative analysis of hepatobiliary transporter activity (2018)
  • Author(s): Takayoshi Nakaoka, Ken-ichi Kaneko, Satsuki Irie, Emi Yamano, Yasuhiro Wada, Aya Mawatari, Ami Igesaka, Hisashi Doi, Yuta Uetake, Hidenori Ochiai, Takashi Niwa, Takamitsu Hosoya, Masaaki Tanaka, Kohei Kotani, Joji Kawabe, Yuichi Sugiyama, Yasuyoshi Watanabe.
  • Organizer: 2018 International Meeting on 22nd MDO and 33rd JSSX
  • Int'l Joint Research