Maitre P O, Vozeh S, Heykants J, Thomson D A, Stanski D R
Anesthesiology. 1987 Jan;66(1):3-12.
The population pharmacokinetic parameters describing the plasma concentration versus time profile of alfentanil in patients undergoing general anesthesia were determined from 614 plasma concentration measurements collected in four previously reported studies with a total of 45 patients. A nonlinear regression analysis evaluating the effect of six concomitant variables revealed a significant influence of body weight on the volume of the central compartment (Vc), and a decrease with age of total body clearance (CL) and of redistribution rate from the deep compartment (k31). A small but significant effect of sex on the Vc was also observed. The duration of anesthesia and the concomitant administration of inhalational anesthetics had no effect on alfentanil pharmacokinetic parameters. The mean CL and Vc for alfentanil in a 70-kg male, aged less than 40 yr, were estimated as 0.356 l/min and 7.77 l, respectively. After correction for age, body weight, and sex, the remaining interindividual variability of alfentanil kinetics (expressed as coefficient of variation) was 48% for CL and 33% for Vc. These population pharmacokinetic parameter estimates should increase the accuracy of predicting concentration-time profiles for intravenous alfentanil infusions. A computer program is presented that allows prediction of the alfentanil plasma concentration and the 68% interval limits of the prediction from the study data analysis.
描述全麻患者中阿芬太尼血药浓度随时间变化曲线的群体药代动力学参数，是根据此前四项研究中收集的614次血药浓度测量值确定的，这四项研究共有45例患者。一项评估六个伴随变量影响的非线性回归分析显示，体重对中央室容积（Vc）有显著影响，总体清除率（CL）和从深部室的再分布率（k31）随年龄增长而降低。还观察到性别对Vc有微小但显著的影响。麻醉持续时间和吸入麻醉药的同时使用对阿芬太尼药代动力学参数没有影响。估计一名体重70kg、年龄小于40岁的男性患者阿芬太尼的平均CL和Vc分别为0.356 l/min和7.77 l。在对年龄、体重和性别进行校正后，阿芬太尼动力学的个体间剩余变异性（以变异系数表示）CL为48%，Vc为33%。这些群体药代动力学参数估计值应能提高预测静脉输注阿芬太尼浓度-时间曲线的准确性。本文介绍了一个计算机程序，该程序可根据研究数据分析预测阿芬太尼血药浓度及预测值的68%区间范围。
