Mechanism for unpredictable drug interaction in patients with chronic kidney disease

• Project/Area Number: 15K08601
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Tsujimoto Masayuki 京都薬科大学, 薬学部, 講師 (90372739)
• Co-Investigator(Kenkyū-buntansha): 峯垣 哲也 京都薬科大学, 薬学部, 助教 (10549306) ; 西口 工司 京都薬科大学, 薬学部, 教授 (80379437)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 慢性腎臓病 / 薬物代謝酵素 / 薬物トランスポーター / 薬物有害事象 / 有害事象 / 薬物相互作用 / 末期腎不全 / 有機アニオン輸送ポリペプチド / 尿毒症物質 / SN-38 / 末期腎不全患者 / 医薬品相互作用

Outline of Final Research Achievements

This study showed that (1) the possibility that the activity of carboxyl esterase is elevated, (2) the possibility that the function of hepatic uptake transporter (s) such as organic anion transporting polypeptide (OATP) 1B1 is decreased, (3) the possibility that the interaction mediated by OATP1B1 needs to be evaluated for each substrate, since the functional change of OATP1B1 varies depending on the substrate, (4) the possibility that enhancement of myopathy is caused not only by the increase in blood concentration but also by the enhancement of tissue toxicity of toxicity drug in patients with chronic kidney disease.

Research Products

• [Journal Article] Substrate-dependent effects of molecular-targeted anticancer agents on activity of organic anion transporting polypeptide 1B1 (2018)
  • Author(s): Koide Hiroyoshi、Tsujimoto Masayuki、Takeuchi Ai、Tanaka Miyu、Ikegami Yoko、Tagami Mayu、Abe Syoko、Hashimoto Miki、Minegaki Tetsuya、Nishiguchi Kohshi
  • Journal Title: Xenobiotica Volume: in press Issue: 10 Pages: 1059-1071
  • DOI: 10.1080/00498254.2017.1393582
  • Peer Reviewed
• [Journal Article] Evaluation of Trace Elements in Augmentation of Statin-Induced Cytotoxicity in Uremic Serum-Exposed Human Rhabdomyosarcoma Cells (2018)
  • Author(s): Uchiyama Hitoshi、Tsujimoto Masayuki、Shimada Naomi、Tsutsui Koji、Nitta Ayaka、Yoshida Takuya、Furukubo Taku、Izumi Satoshi、Yamakawa Tomoyuki、Tachiki Hidehisa、Minegaki Tetsuya、Nishiguchi Kohshi
  • Journal Title: Toxins Volume: 10 Issue: 2 Pages: 53-53
  • DOI: 10.3390/toxins10020053
  • Peer Reviewed
• [Journal Article] Acceleration of carboxylesterase-mediated activation of irinotecan to SN-38 by serum from patients with end-stage kidney disease (2018)
  • Author(s): Koide Hiroyoshi、Tsujimoto Masayuki、Katsube Yurie、Ochiai Megumi、Hojo Ayako、Furukubo Taku、Izumi Satoshi、Yamakawa Tomoyuki、Shima Daisuke、Minegaki Tetsuya、Nishiguchi Kohshi
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: in press Issue: 6 Pages: 1121-1128
  • DOI: 10.1007/s00280-018-3583-y
  • Peer Reviewed
• [Journal Article] Cooperative inhibitory effects of uremic toxins and other serum components on OATP1B1-mediated transport of SN-38 (2017)
  • Author(s): Yurie Katsube, Masayuki Tsujimoto, Hiroyoshi Koide, Megumi Ochiai, Ayako Hojyo, Kaori Ogawa, Kengo Kambara, Nao Torii, Daisuke Shima, Taku Furukubo, Satoshi Izumi, Tomoyuki Yamakawa, Tetsuya Minegaki, Kohshi Nishiguchi
  • Journal Title: Cancer Chemother Pharmacol Volume: 79 Issue: 4 Pages: 783-789
  • DOI: 10.1007/s00280-017-3276-y
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] OATP1B1を介した基質の取り込みに及ぼす分子標的薬の影響 (2017)
  • Author(s): 田中美優、辻本雅之、小出博義、竹内あい、池上葉子、田上真優、阿部祥子、橋本実季、峯垣哲也、西口工司
  • Organizer: 日本薬学会第137年会
• [Presentation] Effects of uremic serum on statin-induced cytotoxicity and its mechanism (2017)
  • Author(s): Hitoshi Uchiyama, Masayuki Tsujimoto, Tadakazu Shinmoto, Hitomi Ogino, Tomoko Oda, Ayaka Nitta, Koji Tsutsui, Naomi Shimada, Takuya Yoshida, Taku Furukubo, Satoshi Izumi, Tomoyuki Yamakawa, Hidehisa Tachiki, Tetsuya Minegaki, Kohshi Nishiguchi
  • Organizer: 2017AAPS Annual Meeting and Exposition
  • Int'l Joint Research
• [Presentation] 末期腎不全患者においてコルヒチン及びクラリスロマイシンの相互作用が重篤化するメカニズムの解明 (2017)
  • Author(s): 下野香帆、辻本雅之、内山 仁、板谷あゆみ、古久保拓、和泉 智、立木秀尚、山川智之、峯垣哲也、西口工司
  • Organizer: 第38回日本臨床薬理学会学術総会
• [Presentation] The Identification of the Mechanism of Elevated Plasma Concentration of SN-38 in Patients with Endstage Kidney Disease:Focus on Metabolic Enzymes and Transporter in the Liver. (2016)
  • Author(s): Yurie Katsube, Masayuki Tsujimoto, Hiroyoshi Koide, Megumi Ochiai, Ayako Hojyo, Daisuke Shima,Taku Furukubo, Satoshi Izumi, Tomoyuki Yamakawa, Tetsuya Minegaki, Kohshi Nishiguchi
  • Organizer: 2016 AAPS Annual Meeting and Exposition
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] 末期腎不全患者血清を曝露させた大腸がん由来細胞株におけるSN-38感受性の低下 (2016)
  • Author(s): 小澤将一、辻本雅之、内山仁、伊藤なつこ、森下智恵、入江怜祐、坂下透子、山本瑞紀、古久保拓、和泉智、立木秀尚、山川智之、峯垣哲也、西口工司
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-03-27
• [Presentation] アリスキレンの肝消失過程に及ぼす有機アニオン輸送ポリポプチド1B1及び1B3の関与 (2016)
  • Author(s): 入江裕子、辻本雅之、吉田拓弥、藤岡春乃、川上祥代、 中谷沙紀、住本菜摘、須本真理子、中川智加、松本光司、 峯垣哲也、西口工司
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-03-27
• [Presentation] OATP1B1を介したプラバスタチン輸送に及ぼす末期腎不全患者血清の影響 (2015)
  • Author(s): 木村朱李、辻本雅之、内山 仁、結城絵理子、佐伯 崇、吉田拓弥、古久保拓、和泉 智、山川智之、峯垣哲也、西口工司
  • Organizer: 第9回日本腎臓病薬物療法学会学術集会・総会2015
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 2015-10-24