| Project/Area Number |
17K08450
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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 |
Medical pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
HIRATA Sumio 熊本大学, 大学院生命科学研究部(薬), 教授 (10432999)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 薬物吸着 / 血液透析 / AN69 / 陽性荷電薬物 / ビグアナイド薬 / アミノグリコシド薬 / 薬物の透析性 / 薬物動態パラメータ / 回帰式 / 分子量 / 蛋白結合率 / 尿中未変化体排泄率 / 分布容積 / 陰性荷電薬物 / アミノグリコシド系抗菌薬 / 透析膜 / 陰性荷電 / 薬物中毒 |
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| Outline of Final Research Achievements |
It was clarified by various experimental systems that aminoglycoside drugs with positive charge are easily adsorbed on the negatively charged membrane AN69. Similarly, the adsorption rate of metformin, which has a positive charge, was unexpectedly low, but it was suggested that the drug adsorbability is affected not only by the drug's positive charge but also by the drug's hydrophobicity.
Multiple regression analysis by the stepwise method and multiple regression analysis by the stepwise method were carried out by using which pharmacokinetic parameter as an explanatory variable and the drug removal rate as an objective variable, and a simple prediction formula was constructed. In addition, oral formulation was added to enhance the applicability and complete the formula with high predictability R = 0.93, p = 1.79e-6).
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| Academic Significance and Societal Importance of the Research Achievements |
（1）薬物と透析膜の静電的結合を利用して、体内に蓄積した薬物を除去するために特殊な透析膜を使用し、速やかに吸着除去を行い、中毒治療に応用する。アミノグリコシド系抗菌薬の過量投与時の速やかな薬物除去が可能となった。
（2）薬物の動態・物性パラメータと、透析による除去率の関係について理論的に構築し、補正を行うことによって臨床使用可能な高精度な薬物除去率予測式を完成した。これにより治験時に臨床データがほとんどない薬物の透析性を正確に予測することができるようになった。
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