Development of therapeutic drug monitoring for anti-MRSA agents based on qualitative changes in albumin
| Project/Area Number |
17K15512
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Oita University |
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Principal Investigator |
Tanaka Ryota 大分大学, 医学部, 准教授 (30781736)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | アルブミン / ダプトマイシン / タンパク結合 / 質的変動 / 翻訳後修飾 / タンパク結合率 / 抗MRSA薬 / 薬学 |
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| Outline of Final Research Achievements |
The purpose of this study is to clarify the association with a protein binding rate of daptomycin or teicoplanin and qualitative changes of albumin in diabetes or chronic kidney disease, which have an increased prevalence as the population ages. We tried to develop measurement method of total and free daptomycin concentration and calculate the in vitro protein binding rate in assumed disease state of diabetes and chronic kidney disease. The wide range and high throughput method of total and free concentration for daptomycin using ultra-performance liquid chromatography coupled to tandem mass spectrometry was successfully developed. Furthermore, the examination of protein binding in the assumed disease state of diabetes and chronic kidney disease suggested that qualitative changes of albumin in these diseases did not affect the protein binding rate of daptomycin.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で確立したダプトマイシン（DAP）の測定法は総濃度、遊離型濃度ともに過去の報告と比較して検量線範囲が広く、低用量単回投与時のトラフ値も高用量繰り返し投与時の最高血中濃度も測定可能になった。これにより遊離型濃度を指標としたDAPによるTDMが可能となった。また、DAPは臨床で認められる濃度において、タンパク結合率に飽和現象を認めないこと、酸化修飾体や糖化修飾体の増加による構造変化の影響を受けないことが確認された。そのため、糖尿病や慢性腎臓病時にダプトマイシンの遊離型濃度は変動しない可能性が示唆され、アルブミンの質的変動を考慮した投与設計をする必要はないことが明らかとなった。
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Report
(4 results)
Research Products
(8 results)
