Effects of C-reactive protein and nuclear receptors on pharmacokinetics of voriconazole
| Project/Area Number |
18K06778
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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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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
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| Keywords | ボリコナゾール / ボリコナゾールN-オキシド体 / 炎症反応 / CYP2C19遺伝子多型 / 核内受容体遺伝子多型 / C反応性蛋白 / CRP / 核内レセプター / 遺伝子多型 / TDM |
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| Outline of Final Research Achievements |
The effects of polymorphisms of pharmacokinetics‐related genes and the inflammatory response on the ratio of voriconazole (VRCZ) N-oxide to VRCZ (VNO/VRCZ) and steady-state dose-adjusted trough concentrations (C0h/D) of VRCZ were investigated. Results of multiple linear regression analyses demonstrated that the presence of the CYP2C19*1/*1 genotype and the presence of the NR1I2 rs3814057 C/C genotype were independent factors influencing the VNO/VRCZ ratio and C0/D in patients with CRP levels of less than 4 mg/dL. On the contrary, in patients with CRP levels of at least 4 mg/dL, no independent factors were found to affect these.
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| Academic Significance and Societal Importance of the Research Achievements |
抗真菌薬であるボリコナゾールは、血中濃度治療域が狭く、かつ、個体内-個体間変動も大きいため、最適な投与量を決定するのに難渋する。したがって、ボリコナゾールの血中動態に影響を及ぼす要因を特定できれば、投与量の個別化において有用な情報となり得る。本研究を通じ、我々は、CYP2C19遺伝子多型、プレグナンX受容体遺伝子多型、及び炎症反応（CRP）が、ボリコナゾールの血中動態に影響を及ぼすことを明らかにした。これらの結果は、ボリコナゾールの適正使用推進に繋がるものと考えられる。
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Report
(5 results)
Research Products
(5 results)
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[Journal Article] Impact of polymorphisms of pharmacokinetics-related genes and the inflammatory response on the metabolism of voriconazole2022
Author(s)
Naoya Aiuchi, Junichi Nakagawa, Hirotake Sakuraba, Takenori Takahata, Kosuke Kamata, Norihiro Saito, Kayo Ueno, Masahiro Ishiyama, Kazufumi Yamagata, Hiroyuki Kayaba, Takenori Niioka
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Journal Title
Pharmacology Research & Perspectives
Volume: 10 (2)
Issue: 2
DOI
Related Report
Peer Reviewed / Open Access
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