2013 Fiscal Year Final Research Report
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 |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Showa University (2013)
Saitama Medical University (2011-2012) |
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Principal Investigator |
FUJITA Ken-ichi 昭和大学, 腫瘍分子生物学研究所, 准教授 (60281820)
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| 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)
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| Project Period (FY) |
2011 – 2013
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| 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 |
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| 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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[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
Year and Date
20131009-11
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