| 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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