| Project/Area Number |
17K15502
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | Hamamatsu University School of Medicine |
|---|
Principal Investigator |
Yamada Takahiro 浜松医科大学, 医学部附属病院, 薬剤主任 (20793540)
|
|---|
| Project Period (FY) |
2017-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | ボリコナゾール / Nオキシド体 / 皮膚障害 / FMO3 / 光増感作用 / ヒドロキシル体 / 光産生物 / 熱分解物 / 臨床薬学 |
|---|
| Outline of Final Research Achievements |
Voriconazole has adverse effects such as photosensitivity. Voriconazole N-oxide was reported to be a candidate for a dermatopathy. This study aimed to evaluate the influence of FMO3 and CYP2C19, voriconazole metabolic enzymes, genotypes on the plasma disposition of voriconazole. In addition, the effects of UVB irradiation on voriconazole and N-oxides were directly observed. Sixty-five patients receiving oral voriconazole were enrolled. The metabolic ratio to N-oxide was significantly higher in the FMO3 E158K/E308G group than in the wild group. CYP2C19 phenotype did not affect the disposition of voriconazole. N-oxide can be converted to photo-modified N-oxide upon UVB exposure. In conclusion, FMO3 E158K/E308G decreased the plasma concentration of voriconazole through its higher metabolic activity. Photo-modified N-oxide may be an important substance in voriconazole-induced dermatopathy.
|
| Academic Significance and Societal Importance of the Research Achievements |
第3世代のアゾール系抗真菌薬は高い抗真菌活性を有しながら、血中濃度コントロールの難しさや有害作用の観点から免疫不全患者において推奨度が低い現状にある。
本研究により、ボリコナゾールおよびNオキシド体の薬物動態・薬力学的特徴がFMO3の遺伝子多型によって一部解明された点は学術的意義が高い。
また、これまで体内動態の評価にのみ用いられていたNオキシド体の皮膚障害発現との関連性について着目し、光増感作用について証明できた。この点は、今後Nオキシド体を皮膚障害の副作用指標として用いる可能性を示唆できた点で社会的意義が高い。
|
