| 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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