Population pharmacokinetics and pharmacodynamics of intravenous acetaminophen in Japanese patients

Research Project

Project/Area Number	15K20052
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Anesthesiology
Research Institution	Fukushima Medical University
Principal Investigator	Obara Shinju 福島県立医科大学, 医学部, 准教授 (00443854)
Project Period (FY)	2015-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2018: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000) Fiscal Year 2017: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000) Fiscal Year 2016: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000) Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords	アセトアミノフェン / 薬物動態 / 日本人
Outline of Final Research Achievements	A population pharmacokinetic model of i.v.acetaminophen in Japanese patients that can be used for simulations of blood concentrations was constructed, with performance within acceptable ranges. The pharmacokinetics of i.v. acetaminophen were described with body weight as a covariate. After the evaluation of previously published pharmacokinetic models, we concluded that ethnical differences did not affect the prediction of the pharmacokinetic model with a compartment structure. The amount of fentanyl requirement during first 6 hours after the surgery did not show the statistically significant differences between two infusion durations (i.e., 60 min vs 120 min) of acetaminophen. Predicted blood concentrations of acetaminophen and effect site concentrations of fentanyl correlated positively and significantly.
Academic Significance and Societal Importance of the Research Achievements	これまで発表されていなかった日本人の成人患者を母集団とする、静脈注射用アセトアミノフェンのコンパートメントモデルを発表した。日本人とこれまで発表された外国人において、アセトアミノフェンの薬物動態モデル構造に大きな差がないことが判明した。今回作成した薬物動態モデルを用いることで、アセトアミノフェンの投与履歴から薬物血中濃度を推定可能になった。加えて、アセトアミノフェンの適切な投与計画を立てるためのシミュレーション等、広く使用が可能である。