Exploration of blood marker that enable prediction of drug permeation through blood brain barrier

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16406
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Chiba University
• Principal Investigator: Ishikawa Masayuki 千葉大学, 大学院薬学研究院, 助教 (40824561)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 血液脳関門 / 血液マーカー / 中枢移行性

Outline of Final Research Achievements

We evaluated the association between the blood level of UCHL1 and GFAP in 21 patients with bacterial meningitis and cerebrospinal fluid protein/serum albumin ratio (CSF-P/SA ratio) which reflects the extent of BBB disruption. The blood level of UCHL1 and GFAP did not show a significant association with CSF-P/SA ratio. Thus, we could not find a blood marker that enable prediction of BBB permeability in this study.
On the other hand, we showed that CSF-P/SA ratio × vancomycin (VCM) serum trough concentration/VCM minimum inhibitory concentration (MIC) could be associated with microbiological efficacy of VCM for bacterial meningitis. This indicates that the extent of BBB disruption could be associated with microbiological efficacy of VCM in the patients with bacterial meningitis as well as VCM serum trough concentration and MIC.

Free Research Field

薬物動態

Academic Significance and Societal Importance of the Research Achievements

本研究により、細菌性髄膜炎に対するバンコマイシン (VCM)の微生物学的有効性に、薬物の脳移行を制御する血液脳関門の透過性の変動が関与する可能性が示された。初期の抗菌薬治療の失敗が予後の悪化を招くと言われる細菌性髄膜炎の治療において、治療開始前の検査結果よりVCMの脳移行性を予測し、治療に活用することで細菌性髄膜炎の予後の改善につながる可能性がある。今後はVCM以外の薬物についても同様の検討を行うとともに血液脳関門の透過性の変動を簡便に予測できる血液マーカーについてさらなる検討を行うことで、脳における薬物の有効性や安全性の向上につながる可能性がある。