Eleveld Douglas J, Proost Johannes H, Vereecke Hugo, Absalom Anthony R, Olofsen Erik, Vuyk Jaap, Struys Michel M R F
Department of Anesthesiology, University Medical Center Groningen, University of Groningen, The Netherlands (D.J.E., J.H.P., H.V., A.R.A., M.M.R.F.S.); Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands (E.O., J.V.); and Department of Anesthesia, Ghent University, Gent, Belgium (M.M.R.F.S.).
Anesthesiology. 2017 Jun;126(6):1005-1018. doi: 10.1097/ALN.0000000000001634.
Pharmacokinetic and pharmacodynamic models are used to predict and explore drug infusion schemes and their resulting concentration profiles for clinical application. Our aim was to develop a pharmacokinetic-pharmacodynamic model for remifentanil that is accurate in patients with a wide range of age and weight.
Remifentanil pharmacokinetic data were obtained from three previously published studies of adults and children, one of which also contained pharmacodynamic data from adults. NONMEM was used to estimate allometrically scaled compartmental pharmacokinetic and pharmacodynamic models. Weight, age, height, sex, and body mass index were explored as covariates. Predictive performance was measured across young children, children, young adults, middle-aged, and elderly.
Overall, 2,634 remifentanil arterial concentration and 3,989 spectral-edge frequency observations from 131 individuals (55 male, 76 female) were analyzed. Age range was 5 days to 85 yr, weight range was 2.5 to 106 kg, and height range was 49 to 193 cm. The final pharmacokinetic model uses age, weight, and sex as covariates. Parameter estimates for a 35-yr-old, 70-kg male (reference individual) are: V1, 5.81 l; V2, 8.82 l; V3, 5.03 l; CL, 2.58 l/min; Q2, 1.72 l/min; and Q3, 0.124 l/min. Parameters mostly increased with fat-free mass and decreased with age. The pharmacodynamic model effect compartment rate constant (ke0) was 1.09 per minute (reference individual), which decreased with age.
We developed a pharmacokinetic-pharmacodynamic model to predict remifentanil concentration and effect for a wide range of patient ages and weights. Performance exceeded the Minto model over a wide age and weight range.
药代动力学和药效学模型用于预测和探索药物输注方案及其临床应用中产生的浓度曲线。我们的目标是开发一种在年龄和体重范围广泛的患者中准确的瑞芬太尼药代动力学-药效学模型。
瑞芬太尼药代动力学数据来自之前发表的三项成人和儿童研究，其中一项还包含成人的药效学数据。使用NONMEM来估计按体表面积缩放的房室药代动力学和药效学模型。将体重、年龄、身高、性别和体重指数作为协变量进行探索。在幼儿、儿童、青年、中年和老年人中测量预测性能。
总体而言，分析了来自131名个体（55名男性，76名女性）的2634次瑞芬太尼动脉浓度和3989次频谱边缘频率观察值。年龄范围为5天至85岁，体重范围为2.5至106千克，身高范围为49至193厘米。最终的药代动力学模型使用年龄、体重和性别作为协变量。一名35岁、70千克男性（参考个体）的参数估计值为：V1，5.81升；V2，8.82升；V3，5.03升；CL，2.58升/分钟；Q2，1.72升/分钟；Q3，0.124升/分钟。参数大多随去脂体重增加而增加，随年龄增加而降低。药效学模型效应室速率常数（ke0）为每分钟1.09（参考个体），随年龄降低。
我们开发了一种药代动力学-药效学模型，以预测广泛年龄和体重范围患者的瑞芬太尼浓度和效应。在广泛的年龄和体重范围内，其性能超过了Minto模型。
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