A new three compartment model incorporated with dilution process

三房室药代动力学（PK）模型常用于解释静脉给药的药物吸收和处置过程。在该模型中，假设在药物进入血液循环后立即发生瞬时稀释，但我们进行了一些研究，其中该假设被证明是错误的，需要一定的稀释时间来符合中央室的均匀分布。这种零假设可能会误导血药浓度时间曲线的正确估计，特别是在推注给药或大剂量恒定输注后的二阶瞬态期间。我们将稀释过程模型与三房室模型（混合模型）相结合，尝试估算瞬态期、中、缓降期的血清浓度，以确定药代动力学时间曲线中的分布和消除相。采用异氟醚和异丙酚复合麻醉， ...更多信息 以2 mg/kg/min的快速输注速率给药5分钟。输注结束后，将猪麻醉至135分钟。在整个研究期间，在输注持续期和输注终止期均按预定时间间隔采集血样。血样经离心分离血清，用高效液相色谱法进行分析。平均合并数据用于通过使用最小二乘法估计PK常数和稀释模型常数。结果<all><rpd>表明，<all>新混合模型和传统三室模型的EP_分别为155.0和207.7（mcg/ml）^2，EP_分别<rpd>为97.7和197.8（mcg/ml）^2，新混合模型能更准确地估计药物在快速转换期、缓慢分布期和消除期的浓度-时间曲线。少

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