A General Purpose Pharmacokinetic Model for Propofol
A General Purpose Pharmacokinetic Model for Propofol
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DOI：
10.1213/ane.0000000000000165
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发表时间：
2014-06-01
影响因子：
5.7
通讯作者：
Struys, Michel M. R. F.
中科院分区：
文献类型：
--
作者：
Eleveld, Douglas J.;Proost, Johannes H.;Struys, Michel M. R. F.
背景：药代动力学（PK）模型用于预测术中显示输注方案的药物浓度，并计算靶控输注系统中的输注速率。对于异丙酚，文献中可用的PK模型大多是根据特定的患者群体或麻醉技术开发的，在不同的患者和临床条件下，模型的准确性存在不确定性。我们的目标是确定一个具有强大预测性能的PK模型，适用于广泛的患者群体和临床状况。方法：我们汇总并分析了21个先前发表的异丙酚数据集，其中包含来自幼儿、儿童、成人、老年人和肥胖个体的数据。以体重、年龄、性别和患者状态为协变量，用NONMEM软件估计3室异速生长模型。我们设计了一种以术中情况为重点的预测性能指标，并与赤池信息标准一起使用，以指导模型的开发。结果：该数据集包含660名个体（年龄范围0.25-88岁，体重范围5.2-160 kg）的10,927个药物浓度观察结果。最后一个模型使用体重、年龄、性别和患者与健康志愿者作为协变量。35岁，体重70公斤的男性患者的参数估计值分别为：V1， V2, V3， CL， Q2和Q3的9.77,29.0,134 L, 1.53, 1.42和0.608 L/min。预测性能优于或类似于专门的模型，甚至对那些模型派生的亚种群也是如此。结论：我们开发了一种单一异丙酚PK模型，该模型在广泛的患者群体和临床条件下表现良好。需要对该模型进行进一步的前瞻性评价。
BACKGROUND: Pharmacokinetic (PK) models are used to predict drug concentrations for infusion regimens for intraoperative displays and to calculate infusion rates in target-controlled infusion systems. For propofol, the PK models available in the literature were mostly developed from particular patient groups or anesthetic techniques, and there is uncertainty of the accuracy of the models under differing patient and clinical conditions. Our goal was to determine a PK model with robust predictive performance for a wide range of patient groups and clinical conditions.METHODS: We aggregated and analyzed 21 previously published propofol datasets containing data from young children, children, adults, elderly, and obese individuals. A 3-compartmental allometric model was estimated with NONMEM software using weight, age, sex, and patient status as covariates. A predictive performance metric focused on intraoperative conditions was devised and used along with the Akaike information criteria to guide model development.RESULTS: The dataset contains 10,927 drug concentration observations from 660 individuals (age range 0.25-88 years; weight range 5.2-160 kg). The final model uses weight, age, sex, and patient versus healthy volunteer as covariates. Parameter estimates for a 35-year, 70-kg male patient were: 9.77, 29.0, 134 L, 1.53, 1.42, and 0.608 L/min for V1, V2, V3, CL, Q2, and Q3, respectively. Predictive performance is better than or similar to that of specialized models, even for the subpopulations on which those models were derived.CONCLUSIONS: We have developed a single propofol PK model that performed well for a wide range of patient groups and clinical conditions. Further prospective evaluation of the model is needed.