Elucidation of the clinical significance of drug interactions mediated by ABCG2 inhibition on hematopoietic stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15293
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: The University of Tokyo
• Principal Investigator: Miyata Hiroshi 東京大学, 医学部附属病院, 助教 (90844415)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 薬物相互作用 / ABCG2 / 抗がん剤 / 腫瘍崩壊症候群

Outline of Final Research Achievements

ABCG2 is a transporter responsible for controlling the pharmacokinetics and toxicity of drugs. The purpose of this study was to clarify the clinical importance of ABCG2 inhibition by the uric acid-lowering drug febuxostat (FEB) from the perspective of adverse events.
We investigated the frequency and intensity of myelosuppression by combination therapy of cyclophosphamide, doxorubicin, vincristine, and prednisolone with/without FEB at the University of Tokyo Hospital. As a result, there was no significant differentce between the group. However, interestingly, bone marrow suppression was observed to be enhanced when combined with rasburicase, a uric acid metabolic enzyme.

Free Research Field

医療系薬学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、FEBはCHOP療法施行患者であっても有害事象の頻度や強度を有意に増強することなく併用可能であることが示唆された。その他のABCG2基質薬物を含む治療に対するFEBの影響は今後の検討課題である。一方で、FEBと同様に腫瘍崩壊症候群に対して用いられるラスブリカーゼがCHOP療法による骨髄抑制を増強する可能性が示唆された。骨髄抑制は抗がん剤治療の継続や治療強度、ひいては治療の成否に影響を与える重要な要素であり、そのリスクの解明につながる重要な知見である。