Mechanisms of delayed elimination and decreased plasma protein binding of anticancer drugs which are mainly eliminated via the liver in cancer patients with severe renal failure
| Project/Area Number |
26460205
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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 |
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Principal Investigator |
Fujita Ken-ichi 昭和大学, 腫瘍分子生物学研究所, 教授 (60281820)
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| Co-Investigator(Renkei-kenkyūsha) |
KATO Yukio 金沢大学, 薬学系, 教授 (30251440)
SASAKI Yasutsuna 昭和大学, 医学部, 教授 (20235279)
ANDO Yuichi 名古屋大学, 医学部, 教授 (10360083)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 腎機能障害 / 肝消失型抗がん薬 / イリノテカン / 薬物動態 / SN-38 / 蛋白結合 / PBPKモデル / 投与設計 / 肝代謝型 / 尿毒素 / indole / long-lasting inhibition / イリノテカン塩酸塩 / 遊離形 |
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| Outline of Final Research Achievements |
The area under the plasma unbound concentration-time curve (AUCu) of SN-38 in patients with severe renal failure was 4.38-fold higher than that in normal kidney patients. This might be a cause of prolonged neutropenia observed in these patients. Decreased hepatic uptake clearance of SN-38 and the higher unbound fraction of SN-38, partly because of the inhibition of SN-38 protein binding by uremic toxins might be causes for the high AUCu of SN-38 in such patients. PBPK modeling indicated substantially reduced influx of SN-38 into hepatocytes and approximately one-third irinotecan dose for patients with severe renal failure to produce an unbound concentration profile of SN-38 similar to normal kidney patients.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Increased plasma concentrations of unbound SN-38, the active metabolite of irinotecan, in cancer patients with severe renal failure2016
Author(s)
Ken-ichi Fujita, Yusuke Masuo, Hidenori Okumura, Yusuke Watanabe, Hiromichi Suzuki, Yu Sunakawa, Ken Shimada, Kaori Kawara, Yuko Akiyama, Masanori Kitamura, Munetaka Kunishima, Yasutsuna Sasaki, Yukio Kato
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Journal Title
Pharmaceutical Research
Volume: 33
Issue: 2
Pages: 269-282
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Change in plasma protein binding of SN-38, an active metabolite of irinotecan, in cancer patients with severe renal failure (SRF).2014
Author(s)
Ken-ichi Fujita, Hidenori Okumura, Yusuke Masuo, Yu Sunakawa, Ken Shimada, Kaori Kawara, Yuko Akiyama, Yasutsuna Sasaki, Yukio Kato
Organizer
The 39th European Society for Medical Oncology annual meeting
Place of Presentation
Madrid
Year and Date
2014-09-27 – 2014-09-30
Related Report
