Optimized Dosage of Dexmedetomidine Based on its Pharmacological Activity in Post-surgical Patients

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K18936
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Yagi Tatsuya 浜松医科大学, 医学部附属病院, 薬剤師 (70719575)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: デクスメデトミジン / 術後患者 / 薬物動態

Outline of Final Research Achievements

Thirty-three post-surgical patients receiving continuous intravenous dexmedetomidine were enrolled. Blood specimens and clinical data (included RCSQ) were sampling 12-h after starting administration of dexmedetomidine. The medians (interquartile range) of the concentration, area under the concentration;time curve of dexmedetomidine from 0 to 12 h (AUC0-12), apparent elimination half-life, distribution volume, and total clearance were 0.54 ng/mL (0.37, 0.64 ng/mL), 4.27 ng h/mL (2.92, 5.60 ng h/mL), 5.72 h (5.23, 6.22 h), 228 L (160, 313 L) and 29.4 mL/h (21.2, 37.0 mL/h), respectively. Distribution volume and total clearance of dexmedetomidine were correlated with the elevation ratio of creatinine clearance. The medians (interquartile range) of RCSQ were 66.2（32.4, 87.8）mean mm, and AUC and plasma concentration of dexmedetomidine were higher in patients with above 76 mean mm for RCSQ.

Free Research Field

臨床薬理学

Academic Significance and Societal Importance of the Research Achievements

健常成人でのデクスメデトミジンの体内動態については明らかとなっているが、デクスメデトミジンの主な投与患者群である術後患者における体内動態の評価は乏しい。本研究の特色としては、心臓血管外科手術などの大侵襲手術を含む患者を対象としたことにある。術後患者におけるデクスメデトミジンの体内動態およびその変動要因を解明した点、血中デクスメデトミジン濃度と精神神経保護効果との関連を明らかにした点は、臨床現場において問題となっている術後せん妄の発症予防や体内動態変動を考慮したデクスメデトミジンの最適な投与方法の開発につながる。また、術後せん妄をはじめとする他の精神疾患の治療の研究に発展する可能性がある。