• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2021 Fiscal Year Final Research Report

Establishment of optimal combination of novel inhibitors of uric acid production and purine analogs based on intracellular molecular pharmacology

Research Project

  • PDF
Project/Area Number 16K18935
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionUniversity of Fukui

Principal Investigator

Morita Mihoko  福井大学, 学術研究院医学系部門, 助教 (40623872)

Project Period (FY) 2016-04-01 – 2022-03-31
Keywords薬物相互作用 / XOD阻害薬 / XOD活性
Outline of Final Research Achievements

The cell proliferation inhibitory effect of Febuxostat (FEB), an inhibitor of uric acid production, and 6MP, a purine analog in combination, was confirmed in leukemia cells. The CI value was 0.114, showed a clear synergistic effect. This study showed the strong temporal XOD inhibitory effect of FEB at 24 h. XOD activity was confirmed under the 6MP combination condition, suggesting that 6MP itself has no effect on XOD activity. Cell viability experiments showed that FEB was not cytotoxic, suggesting that the combination of 6MP and FEB enhanced the cytotoxicity of 6MP. There are interactions when these drugs are used in combination, and caution should be exercised.

Free Research Field

血液・腫瘍内科 腫瘍崩壊症候群 痛風

Academic Significance and Societal Importance of the Research Achievements

高尿酸血症治療薬であるxanthine oxidase(XOD)阻害薬はプリン代謝を阻害することで尿酸生成を抑制する。そのためアロプリノールとプリンアナログとの併用時には、減量規定に基づきプリンアナログの投与量を調節する。しかし、2011年に本邦にて上市されたフェブキソスタットとプリンアナログとの併用についてはその至適減量基準は確立されていなかった。本研究では、フェブキソスタットと代表的プリンアナログ、6メルカプトプリン(6-MP)との相互作用について、培養白血病細胞を用いて分子薬理学的に検討し、相乗効果を示すことを明らかにした。

URL: 

Published: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi