2022 Fiscal Year Final Research Report
Clinical pharmacokinetic analysis of antibody drugs by application of innovative measurement techniques directed to personalized medicine
| Project/Area Number |
20K07157
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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 | Gifu Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大野 康 朝日大学, 歯学部, 教授 (00334938)
平井 啓太 信州大学, 医学部, 准教授 (30740203)
飯原 大稔 岐阜薬科大学, 薬学部, 研究員 (40775095)
轟木 堅一郎 静岡県立大学, 薬学部, 教授 (70341451)
鈴木 昭夫 岐阜大学, 医学部附属病院, 准教授 (80775148)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 抗体医薬 / 血漿中濃度 / 個別化薬物療法 |
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| Outline of Final Research Achievements |
In this study, we developed an anti-idiotypic DNA aptamer that selectively recognizes antibody drugs such as pertuzumab and rituximab, and evaluated the acquired aptamer and studied it for measurement of drug concentration in blood. The acquired aptamer had high binding affinity and specificity to selectively capture only the target substance from IgG in blood.
Furthermore, to clarify the relationship between the pharmacokinetics of antibody drugs and their efficacy and side effects, plasma concentrations were measured in nivolumab-treated patients. In relation to tumor growth and irAE expression, plasma concentrations tended to be higher in the group of patients without tumor growth compared to the group of patients with tumor growth. No differences in plasma concentrations were observed between the different dosing regimens.
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| Free Research Field |
臨床薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において構築した抗体医薬の正確かつ頑健性の高い血中薬物濃度分析法は、TDM、PK/PD解析、バイオシミラー開発時の生物学的同等性評価など様々な用途が考えられ、個別化薬物療法への貢献も期待される。
また、抗体医薬の実臨床での体内動態に関する情報は少なく、本研究の結果から、irAE発現に及ぼすニボルブマブ血漿中濃度の影響は少なく、投与レジメン毎の血漿中濃度は同程度であることが示された。従って、いずれのレジメンも有効性・安全性の点で同等なものとして患者背景を考慮した選択ができると考えられる。また、血漿中濃度を精密にコントロールすることで、さらなる生存期間の延長が期待できる可能性も考えられた。
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