| Project/Area Number |
15K10762
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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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| Research Field |
Otorhinolaryngology
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| Research Institution | Keio University |
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Principal Investigator |
Kanzaki Sho 慶應義塾大学, 医学部(信濃町), 講師 (50286556)
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| Co-Investigator(Kenkyū-buntansha) |
藤岡 正人 慶應義塾大学, 医学部(信濃町), 講師 (70398626)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 内耳 / 薬物動態 / 局所投与 / ドラッグデリバリー / ドラッグデリバリーシステム |
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| Outline of Final Research Achievements |
We used a new in vivo imaging system to compare the pharmacokinetics of combined therapy (CT), with intravenous (IV) or transtympanic (TT) injection alone in both ears of transgenic GFAP-Luc mice. Biological half-life, total photon counts and the area under the curve (AUC) value significantly increased after CT. However, adding IV to TT injection cannot strengthen the peak photon of the drug in the inner ear. In addition, the volume of total photon count and AUC value of CT-left ear are larger than the combined volume of TT-left ear and IV-left ear, suggesting a synergistic effect, and those of CT-right ear are almost equal to the summation of those of IV-right group and TT-right group, suggesting no amplifying effect on the risk of systemic side effect. This study showed that CT could deliver more drugs into the inner ear, and brought a longer therapeutic window, and were more effective than intravenous or transtympanic injection alone in the pharmacokinetics.
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| Academic Significance and Societal Importance of the Research Achievements |
内耳性障害による難聴は難治性である。内耳への治療として、ステロイドの全身投与に加えて局所投与が効果的である、という報告が散見される。一方、内耳薬物動態については不明である。今回、生体モニタリングを用いて内耳薬物動態を解析し、併用投与の方が好ましいという結論に至ったことは今後の難聴治療を変革させるという点で学術的意義がある。アメリカの突発性難聴ガイドラインの解説では、本研究成果を用いた神﨑の過去論（Kanzaki S et al.PLoS one 2014) が引用されており、局所投与を推奨している。WHOによれば難聴はQOLを阻害する7番目の症状であり、その治療は社会的インパクトがある。
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