Schüttler J, Ihmsen H
Department of Anesthesiology, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany.
Anesthesiology. 2000 Mar;92(3):727-38. doi: 10.1097/00000542-200003000-00017.
Target-controlled infusion is an increasingly common type of administration for propofol. This method requires accurate knowledge of pharmacokinetics, including the effects of age and weight. The authors performed a multicenter population analysis to quantitate the effects of covariates.
The authors analyzed 4,112 samples of 270 individuals (150 men, 120 women, aged 2-88 yr, weighing 12-100 kg). Population pharmacokinetic modeling was performed using NONMEM (NONMEM Project Group, University of California, San Francisco, CA). Inter- and intraindividual variability was estimated for clearances and volumes. The effects of age, weight, type of administration and sampling site were investigated.
The pharmacokinetics of propofol were best described by a three-compartment model. Weight was found to be a significant covariate for elimination clearance, the two intercompartmental clearances, and the volumes of the central compartment, the shallow peripheral compartment, and the deep peripheral compartment; power functions with exponents smaller than 1 yielded the best results. The estimates of these parameters for a 70-kg adult were 1.44 l/min, 2.25 l/min, 0.92 l/min, 9.3 l, 44.2 l, and 266 l, respectively. For patients older than 60 yr the elimination clearance decreased linearly. The volume of the central compartment decreased with age. For children, all parameters were increased when normalized to body weight. Venous data showed a decreased elimination clearance; bolus data were characterized by increases in the volumes of the central and shallow peripheral compartments and in the rapid distribution clearance (Cl2) and a decrease in the slow distribution clearance (Cl3).
Pharmacokinetics of propofol can be well described by a three-compartment model. Inclusion of age and weight as covariates significantly improved the model. Adjusting pharmacokinetics to the individual patient should improve the precision of target-controlled infusion and may help to broaden the field of application for target-controlled infusion systems.
靶控输注是丙泊酚越来越常用的一种给药方式。这种方法需要准确了解药代动力学，包括年龄和体重的影响。作者进行了一项多中心群体分析，以量化协变量的影响。
作者分析了270名个体（150名男性，120名女性，年龄2至88岁，体重12至100千克）的4112份样本。使用NONMEM（加利福尼亚大学旧金山分校NONMEM项目组）进行群体药代动力学建模。估计清除率和容积的个体间和个体内变异性。研究年龄、体重、给药类型和采样部位的影响。
丙泊酚的药代动力学最好用三室模型来描述。发现体重是消除清除率、两个室间清除率以及中央室、浅周边室和深周边室容积的显著协变量；指数小于1的幂函数产生了最佳结果。一名70千克成年人这些参数的估计值分别为1.44升/分钟、2.25升/分钟、0.92升/分钟、9.3升、44.2升和266升。对于60岁以上的患者，消除清除率呈线性下降。中央室的容积随年龄减小。对于儿童，所有参数按体重归一化后均增加。静脉数据显示消除清除率降低；推注数据的特征是中央室和浅周边室的容积以及快速分布清除率（Cl2）增加，而缓慢分布清除率（Cl3）降低。
丙泊酚的药代动力学可用三室模型很好地描述。将年龄和体重作为协变量纳入显著改善了模型。根据个体患者调整药代动力学应可提高靶控输注的精度，并可能有助于拓宽靶控输注系统的应用领域。
