Pharmacogenetic study on anti-hepatitis C drugs based on CYP3A5 polymorphisms
| Project/Area Number |
16K18955
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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 | Okayama University (2017-2018)
International University of Health and Welfare (2016) |
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Principal Investigator |
Matsumoto Jun 岡山大学, 医歯薬学総合研究科, 助教 (60709012)
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| Research Collaborator |
Ariyoshi Noritaka 岡山大学大学院, 医歯薬学総合研究科(薬学系), 教授 (00243957)
Fujiyoshi Masachika 岡山大学大学院, 医歯薬学総合研究科(薬学系), 准教授 (50751921)
Nakamura Hiroyoshi 国際医療福祉大学, 薬学部, 教授
Yamada Harumi 国際医療福祉大学, 薬学部, 教授 (70433620)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | CYP3A5 / CYP3A5*3 / CYP3A4 / 薬理遺伝学 / 薬物動態学 / C型肝炎 / HCV / C型肝炎治療薬 / Direct Acting Antiviral / 遺伝子多型 / Direct Acting Antivirals / 薬学 |
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| Outline of Final Research Achievements |
Hepatitis C is a liver disease that is caused by blood-borne viral infection. Several direct-acting antiviral agents (DAAs) have been developed to treat Hepatitis C, which have sustained virological response rates against HCV genotypes 1a and 1b over 90 percent. It is desirable to select the best DAA regimen for each case, as the costs of DAAs are usually high, and treatment failure by a DAA regimen may promote drug-resistant strains. In this study, we have focused on cytochrome P450 (CYP) 3A5 and have investigated the impact of CYP3A5 polymorphisms on four DAAs, asunaprevir, daclatasvir, beclabuvir, and paritaprevir metabolism. Our results have shown that the CYP3A5 has an mportant role in asunaprevir metabolism, but not in daclatasvir, beclabuvir, and paritaprevir metabolism. The findings of the present study may provide foundational information on DAAs metabolism by CYP3As, and may be useful for dosing practices in HCV-infected patients based on CYP3A5 polymorphisms.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、多くの新規C型肝炎治療薬が上市されたが、それらの効果の個人差を規定することができる明確な因子は特定されていない。本研究の成果により、CYP3A5遺伝情報が一部の新規C型肝炎治療薬の個人差を規定できる要因となり得ることが初めて明らかになった。また、本研究では対象としなかった他のC型肝炎治療薬についてもCYP3A5遺伝情報が有用である可能性もあり、今後CYP3A5遺伝子型に基づいて各患者の薬物治療の個別適正化が図れる可能性が考えれられた。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] A proposed simple screening method to determine relative contributions of CYP3A4 and CYP3A5 to drug metabolism in vitro2019
Author(s)
Jun Matsumoto, Hiroyoshi Nakamura, Su Nwe San, Hikari Sato, Manami Takezawa, Ryuto Kishi, Yutaro Kito, Junko Sugano, Mai Izuki, Nao Yanagisawa, Naoki Ikeda, Yusuke Saito, Yoshinori Kato, Harumi Yamada, Masachika Fujiyoshi, and Noritaka Ariyoshi
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Journal Title
Personalized Medicine Universe
Volume: 印刷中
Related Report
Peer Reviewed
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[Presentation] Contribution of CYP3A5 to the metabolism of direct acting anti-hepatitis C virus drugs asunaprevir, daclatasvir, and beclabuvir (Ximency) in vitro2018
Author(s)
Jun Matsumoto, Su New San, Ayano Kawauchi, Shiho Yanaka, Natsumi Chiba, Ran Tagai, Ryoko Sanbe, Masachika Fujiyoshi, Harumi Yamada, and Noritaka Ariyoshi
Organizer
The 24th International Congress of Personalized Medicine
Related Report
Int'l Joint Research
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