2022 Fiscal Year Final Research Report
Prediction system of risk assessments by change the drug metabolism activity in placenta for pregnancy
| Project/Area Number |
20K07139
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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 | Showa Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山崎 浩史 昭和薬科大学, 薬学部, 教授 (30191274)
清水 万紀子 昭和薬科大学, 薬学部, 准教授 (90307075)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | ヒト幹細胞 / BeWo細胞 / 胎盤透過性 / レナリドマイド / 膜透過 |
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| Outline of Final Research Achievements |
The quantitative extrapolation of the effective dose from in vitro to in vivo is of increasing importance. For developmental toxicity this requires scaling the in vitro observed dose-response characteristics to in vivo fetal exposure, in particular transplacental transfer. Transplacental transfer of toxicants can be studied with the use of the BeWo cell, an in vitro model mimicking in vivo transport of a chemical from maternal blood across a cell barrier into the embryo. In this system, hepatocyte cells are co-cultured with BeWo cells to investigate the effects in particular transplacental transfer. This system expect to contribute to a prediction in silico the physiological pharmacokinetics model (PBPK) to the toxicity of chemicals.
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| Free Research Field |
薬物代謝。薬物動態学
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| Academic Significance and Societal Importance of the Research Achievements |
Trans wellを用いたヒト肝細胞と胎盤細胞の共培養系が構築出来たことは、母体が摂取した化合物は胎盤にどのような作用を示すのかを検討する上で、有効活用出来ると共に、その他の細胞の共培養による実験系を提案する事となった。また、生体内の関門である血液脳関門での化合物透過性評価に関して、比較検討した範囲では両者の間に相関性が認められたことから、脳関門透過性評価への応用が期待出来る。今後さらにデーター数を揃えることで、化合物の物性値とともに関門透過性で汎用可能な生理学的薬物動態学 (PBPK）モデルを作成し、薬物・外来性異物の毒性発現をin silicoで予測するのに貢献できる。
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