A new three compartment model incorporated with dilution process

结合稀释过程的新型三室模型

• 批准号: 14571428
• 负责人: MORITA Koji
• 金额: $ 1.66万
• 依托单位: HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571428/
• 关键词: intravenously administered drug; propofol; compartment model; uptake; disposition model; dilution model; target controlled infusion; 3コンパートメントモデル; シーケンシャルコンパートメント; 静脈麻酔薬; 対数正規分布; 直列接続型ミキシングチャンバー

Three compartment pharmacokinetic(PK) model is usually used to explain the uptake and disposition process of intravenously administered drug. In this model the hypothesis that instantaneous dilution would be occurred just after administering the drug into blood circulation, but we had some studies in which that hypothesis showed to be wrong and some dilution time is required to conform uniform distribution in the central compartment. This null-hypothesis might mislead correct estimation of serium concentration time profile especially in the second order transient period after bolus dosing or by large dose constant infusion. We had incorporated a dilution process model with this three compartment model(hybrid model) and had tried to estimate serium concentration in the transient period and in medium and slowly decreasing period such that distribution and elimination phase in pharmacokinetic time profile.We had swine animal study(n=9). They were anesthetized by isoflurane and propofol wa … More s administered for 5 minutes in rapid infusion rate of 2mg/kg/min. After infusion terminated swine were anesthetized until 135 minutes passed. Blood was sampled by predetermined time intervals both in infusion continued and terminated phase throughout study period. Sampled blood was separated to serium by centrifuge and analyzed by high performance liquid, chromatography. Mean pooled data were used to estimate PK constants and dilution model constants by using the least squared method. Estimation performance was compared by calculating summation of the squared difference between estimated and measured data in the range of overall periods(EP_<all>) and in the range of rapid infusion period(EP_<rpd>).EP_<all> in new hybrid model and in conventional three compartment PK model were 155.0 vs 207.7 (mcg/ml)^2 respectively and EP_<rpd> were 97.7 vs 197.8 (mcg/ml)^2 respectively in each model.In conclusion our new hybrid model can estimate more accurately concentration time profile both in rapid transition and slow distribution and elimination phase. Less

三室药代动力学（PK）模型通常用于解释静脉给药的摄取和处置过程。在这个模型中，假设在给药进入血液循环后会发生瞬间稀释，但我们有一些研究表明，这个假设是错误的，需要一些稀释时间才能使中央隔室均匀分布。这种零假设可能会误导对血清浓度时间曲线的正确估计，特别是在大剂量恒定输注后的第二级过渡时期。我们将稀释过程模型与三室模型（混合模型）相结合，并试图估计瞬态和中、慢降期的血清浓度，以便在药代动力学时间剖面中分布和消除阶段。我们进行了猪动物研究（n=9）。用异氟醚和异丙酚麻醉，以2mg/kg/min快速滴注，持续5分钟。输注结束后，猪被麻醉至135分钟。在整个研究期间，在输注继续期和终止期按预定的时间间隔取样。血样经离心分离成血清，高效液相色谱分析。采用平均汇总数据，用最小二乘法估计PK常数和稀释模型常数。通过计算总周期（EP_<all>）和快速输液周期（EP_<rpd>）内估计数据与测量数据的平方差之和来比较估计性能。新混合模型和常规三室PK模型EP_<all>分别为155.0和207.7 (mcg/ml)^2, EP_<rpd>分别为97.7和197.8 (mcg/ml)^2。综上所述，该混合模型可以更准确地估计快速过渡阶段和缓慢分布消除阶段的浓度时间曲线。少

项目成果

Kurita T, Morita K, Kazama T, Sato S: "Comparison of isoflurane and propofol-fentanyl anaesthesia in a swine model of asphyxia."British Journal of Anaesthesia. 91(6). 871-877 (2003)

Kurita T、Morita K、Kazama T、Sato S：“异氟烷和异丙酚-芬太尼麻醉在猪窒息模型中的比较。”英国麻醉杂志。

Kurita T, Morita K, Kazama T, Sato S: "Influence of cardiac output on plasma propofol concentrations during constant infusion in swine"Anesthesiology. 96(6). 1498-1503 (2002)

Kurita T、Morita K、Kazama T、Sato S：“猪持续输注期间心输出量对血浆异丙酚浓度的影响”麻醉学。

Kurita T, Morita K, Kazama T, Sato S: "Influence of cardiac output on plasma propofol concentrations during constant infusion in swine"Anesthesiology. 96(6). 1498-503 (2002)

Kurita T、Morita K、Kazama T、Sato S：“猪持续输注期间心输出量对血浆异丙酚浓度的影响”麻醉学。

Kurita T, Morita K, Kawasaki H, Fujii K: "Lithium dilution cardiac output measurement in oleic acid-induced pulmonary edema"Journal of Cardiothoracic and Vascular Anesthesia. 16(3). 334-337 (2002)

Kurita T、Morita K、Kawasaki H、Fujii K：“油酸引起的肺水肿的锂稀释心输出量测量”心胸和血管麻醉杂志。

Kurita T, Morita K, Kazama T, Sato S: "Comparison of isoflurane and propofol-fentanyl anaesthesia in a swine model of asphyxia"British Journal of Anaesthesia. 91(6). 871-877 (2003)

Kurita T、Morita K、Kazama T、Sato S：“猪窒息模型中异氟烷和异丙酚-芬太尼麻醉的比较”英国麻醉杂志。