Grasela T H, Antal E J, Townsend R J, Smith R B
Clin Pharmacol Ther. 1986 Jun;39(6):605-12. doi: 10.1038/clpt.1986.107.
NONMEM, a computer program that uses the method of extended least-squares analysis, has been advocated as a means of obtaining estimates of population pharmacokinetic parameters when only fragmentary information can be obtained from subjects. To assess the performance of this program, we compared NONMEM with traditional methods for the estimation of population pharmacokinetic parameters with data collected during a phase III clinical trial of alprazolam. NONMEM estimates of the population mean clearance and its coefficient of variation were identical to the estimates obtained with traditional pharmacokinetic techniques. Moreover, NONMEM estimates of these parameters remained stable even when a few as three data points were available per subject. NONMEM estimates of the mean volume of distribution and its coefficient of variation appear to be overestimated, apparently because of the sampling scheme used to generate data for the NONMEM analysis. Suggestions for the effective use of NONMEM in clinical trials, to maximize the benefits of this approach, are provided. Our results lend further support for the use of NONMEM to estimate population pharmacokinetic parameters of a drug from data generated during phase III clinical trials.
NONMEM是一种使用扩展最小二乘法分析方法的计算机程序，当只能从受试者那里获得零碎信息时，它被倡导作为一种获取群体药代动力学参数估计值的方法。为了评估该程序的性能，我们将NONMEM与传统方法进行了比较，后者用于根据阿普唑仑III期临床试验期间收集的数据来估计群体药代动力学参数。NONMEM对群体平均清除率及其变异系数的估计与传统药代动力学技术获得的估计值相同。此外，即使每个受试者仅有三个数据点，这些参数的NONMEM估计值仍保持稳定。NONMEM对平均分布容积及其变异系数的估计似乎被高估了，这显然是由于用于生成NONMEM分析数据的抽样方案所致。本文提供了在临床试验中有效使用NONMEM的建议，以最大化这种方法的益处。我们的结果进一步支持使用NONMEM从III期临床试验期间生成的数据中估计药物的群体药代动力学参数。
