Inhibitory mechanisms of hepatic uptake transporters/OATP during renal failure
| Project/Area Number |
26860099
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
MASUO YUSUKE 金沢大学, 薬学系, 助教 (90708140)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | トランスポーター / 慢性腎障害 / 尿毒素 / 薬物輸送担体 / 薬物代謝酵素 |
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| Outline of Final Research Achievements |
Several uremic toxins have been proposed to inhibit hepatic uptake transporters. The purpose is to clarify possible long-lasting inhibition of OATP1B1 by uremic toxins. OATP1B1-mediated uptake of [3H]estrone sulfate (E3S) was examined after co-incubation or preincubation with uremic toxins in HEK293/OATP1B1 cells and primary cultured human hepatocytes. Among 21 uremic toxins, indoxyl sulfate (IS), CMPF and p-cresyl sulfate directly inhibited OATP1B1 mediated-uptake of E3S, but only IS exhibited inhibitory effect even after preincubation. Such inhibition of E3S uptake by preincubation with IS was more remarkable than that by its co-incubation, and observed in preincubation time- and concentration-dependent manners. Preincubation with IS also decreased uptake of E3S in human hepatocytes in primary culture. Overall, the long-lasting inhibition in the presence of IS could at least partially explain the delayed elimination of OATP1B1 substrate drugs during severe renal failure.
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] Localizatoin of xenobiotic transporter OCTN1/SLC22A4 in hepatic stellate cells and its protective role in liver fibrosis.2016
Author(s)
Tang Y, Masuo Y, Sakai Y, Wakayama T, Sugiura T, Harada R, Futatsugi A, Komura T, Nakamichi N, Sekiguchi H, Sutoh K, Usumi K, Iseki S, Kaneko S, Kato Y.
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Journal Title
J Pharm Sci
Volume: 印刷中
Issue: 5
Pages: 1779-89
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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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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