Establishment of appropriate management of anti-HIV drugs to suppress the onset of HIV-associated neurocognitive disorder (HAND)
Project/Area Number |
18K06747
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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 |
Review Section |
Basic Section 47060:Clinical pharmacy-related
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Research Institution | Kyoto University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
山下 富義 京都大学, 薬学研究科, 教授 (30243041)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 抗HIV薬 / インテグラーゼ阻害薬 / トランスポーター / BCRP / P-gp / 血液脳関門 / HIV関連神経認知障害 / 有害事象自発報告データベース / 脂溶性 / 脳移行 / トランスポータ / HAND |
Outline of Final Research Achievements |
In the present study, we aimed to clarify the involvement of drug efflux transporters in the brain trafficking process of integrase inhibitors, a class of anti-HIV drugs. We showed that dolutegravir and bictegravir are transported by the drug efflux transporter BCRP, and that raltegravir tends to be transported by BCRP. Pharmacokinetic experiments in mice revealed that drug transport via P-gp and BCRP is involved in the transfer of dolutegravir and raltegravir to the brain. These findings may provide useful information for avoiding neuropsychiatric adverse events in HIV infection.
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Academic Significance and Societal Importance of the Research Achievements |
HIVによる神経毒性を原因とするHIV関連神経認知障害(HAND)は、HIV感染患者の生存率の改善に伴い問題となってきている重大な合併症である。HANDの治療や予防において抗HIV薬の脳内への移行性が重要と言われている。本研究で得られた成果は、HIV治療のキードラッグであるインテグラーゼ阻害薬の脳内移行性を評価したものであり、HANDの発症抑制に有効な薬物選択法の構築に貢献するものである。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Analysis of Glycoforms and Amino Acids in Infliximab and a Biosimilar Product Using New Method with LC/TOF-MS2018
Author(s)
Tsuda M, Otani Y, Yonezawa A, Masui S, Ikemi Y, Denda M, Sato Y, Nakagawa S, Omura T, Imai S, Nakagawa T, Hayakari M, Matsubara K.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 41
Issue: 11
Pages: 1716-1721
DOI
ISSN
0918-6158, 1347-5215
Year and Date
2018-11-01
Related Report
Peer Reviewed
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