Mechanism for the delayed elimination of SN-38 in cancer patients with severe renal failure and optimal treatment strategy
Project/Area Number |
23590198
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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 |
Research Field |
Medical pharmacy
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Research Institution | Showa University (2013) Saitama Medical University (2011-2012) |
Principal Investigator |
FUJITA Ken-ichi 昭和大学, 腫瘍分子生物学研究所, 准教授 (60281820)
|
Co-Investigator(Renkei-kenkyūsha) |
SASAKI Yasutsuna 昭和大学, 医学部, 教授 (20235279)
OKAZAKI Yasushi 埼玉医科大学, 医学部, 教授 (80280733)
KATO Yukio 金沢大学, 薬学系, 教授 (30251440)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
|
Keywords | SN-38 / 排泄遅延 / 腎機能低下 / 尿毒素 / OATP1B1 / 発現低下 / 肝消失型抗がん薬 / 蛋白結合 / 肝消失型 / 排出遅延 / 腎機能 / 尿毒症物質 / 腎不全 / イリノテカン / 体内動態 / トランスポーター / UGT1A1 |
Research Abstract |
We have shown for the first time that uremic toxins such as CMPF inhibit SN-38 uptake in human hepatocytes at clinically relevant concentrations. OATP1B1 is a major contributor to the saturable uptake of SN-38 in human hepatocytes. The gene expression of SLCO1B1 was down-regulated by uremic plasma. The inhibition by uremic toxins of OATP1B1-mediated SN-38 uptake and the down-regulated SLCO1B1 gene expressions may be part of the mechanisms causing the delay of SN-38 elimination observed in patients with severe renal dysfunction.
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Report
(4 results)
Research Products
(27 results)
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[Presentation] Direct Inhibition and Down-regulation by Uremic Plasma Components of Hepatic Uptake Transporter for SN-38, an Active Metabolite of Irinotecan, in Humans2013
Author(s)
Okumura H, Fujita K, Masuo Y, Sugiura T, Nakamichi N, Watanabe Y, Suzuki H, Sunakawa Y, Shimada K, Kawara K, Sasaki Y, Kato Y
Organizer
28^<th> Japanese Society for the Study of Xenobiotics annual meeting
Place of Presentation
Tokyo
Related Report
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[Presentation] Direct Inhibition and Down-regulation by Uremic Plasma Components of Hepatic Uptake Transporter for SN-38, an Active Metabolite of Irinotecan, in Humans2013
Author(s)
Hidenori Okumura, Ken-ichi Fujita, Yusuke Masuo, Tomoko Sugiura, Noritaka Nakamichi, Yusuke Watanabe, Hiromichi Suzuki, Yu Sunakawa, Ken Shimada, Kaori Kawara, Yasutsuna Sasaki, Yukio Kato
Organizer
28th Japanese Society for the Study of Xenobiotics annual meeting
Place of Presentation
Tokyo
Related Report
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