Theoretical analysis of efficacy and side effects of direct oral anticoagulants for appropriate anticoagulation therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06716
• 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: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Yasuhiko Yamada 東京薬科大学, 薬学部, 教授 (40158225)
• Co-Investigator(Kenkyū-buntansha): 片桐 文彦 東京薬科大学, 薬学部, 講師 (60420642)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 直接経口抗凝固薬 / 血中濃度 / 比色法

Outline of Final Research Achievements

With the launch of direct oral anticoagulants (DOACs), anticoagulant therapy has become more flexible, moving away from warfarin-based treatment. DOACs were considered safe to use without the need for monitoring or dose adjustment, but in recent years, it has become necessary to reevaluate their use. In this study, we aim to estimate the blood drug concentration range that will serve as an indicator of efficacy and safety, and to develop a simple evaluation method, with the aim of implementing appropriate anticoagulant therapy. By analyzing the results of a phase 3 trial comparing them with warfarin, we were able to estimate the risk range of blood Xa inhibitor concentrations. We also developed a measurement system that can be evaluated using an absorption spectrophotometer, and were able to measure the Xa inhibitor concentration.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

直接経口抗凝固薬はワルファリンと異なり用量調整が不可能である。多くの患者は、常用量で安全かつ有効に使用できるが、高齢者や併用薬が多い患者などは、安全に使用できるとは限らない。本研究の成果は、特に出血リスクが高くなる血中濃度域を明らかにできたため、血中濃度が変化しやすい病態の患者を抽出し、適切な抗凝固療法の施行に貢献できると考えられる。一方、直接経口抗凝固薬の血中濃度測定は液体クロマトグラフィー質量分析計が専らであり、設備の面で測定できる施設はかなり限られる。直接経口抗凝固薬はその血中濃度と標的酵素の阻害活性に相関関係があり、既報の条件を応用することで、特別な設備がなくとも血中濃度を評価できた。