Strategy of personalized drug therapy considering organ crosstalk of drug metabolism and toxicity during liver regeneration

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06750
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Hiroshima University
• Principal Investigator: SANOH Seigo 広島大学, 医系科学研究科(薬), 助教 (00552267)
• Co-Investigator(Kenkyū-buntansha): 古武 弥一郎 広島大学, 医系科学研究科(薬), 教授 (20335649) ; 太田 茂 広島大学, 医系科学研究科(薬), 名誉教授 (60160503)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肝再生 / 臓器間連携 / 薬物代謝 / 毒性

Outline of Final Research Achievements

The studies of drug metabolism and toxicity were conducted using a partial hepatectomy (PH) mouse model for liver regeneration. During the process of hepatic regeneration from hepatectomy, an increase in the expression of cytochrome P450, one of drug-metabolizing enzymes expressed in the small intestine was observed. The finding was considered to be a result of compensatory induction by the organ crosstalk between the liver and small intestine to maintain the function of detoxification due to decreased liver function. In addition, such drugs which alter the ability of liver regeneration may affect the pharmacokinetics and be involved in hepatotoxicity, which requires attention in drug therapy.

Free Research Field

薬物代謝学、毒性学

Academic Significance and Societal Importance of the Research Achievements

肝臓がんの治療において、腫瘍摘出のために、肝臓の再生機能を期待した肝切除術がなされることが多い。肝再生される間も、さまざまな薬物治療がなされることがあるが、肝切除による肝機能低下による薬物動態の変化や副作用発現を考慮した個別化薬物療法の実践が求められる。本研究で得られた、肝再生過程における薬物代謝酵素の臓器間連携や、薬剤の肝再生に与える影響評価に関する知見は、最適な薬物治療の提案に有用となることが期待される。