Flühler H, Huber H, Widmer E, Brechbühler S
Drug Metab Rev. 1984;15(1-2):317-39. doi: 10.3109/03602538409015069.
Ethical issues arising from the use of patients in medical research have stimulated pharmacokinetic research in population kinetics, which requires only a few concentration samples of each individual. Using historical maprotiline data, the new approach of population kinetics was investigated and compared to individually estimated kinetics. Two different population kinetic methods were applied. The naive approach, a quick and dirty method, was compared to the nonlinear mixed-effects method, which was applied by the NONMEM package. Based on the results we obtained from actual maprotiline data as well as from simulated data, NONMEM is a reasonable tool for the estimation of population pharmacokinetic parameters. The main advantage of NONMEM over the naive approach lies in the possibility of obtaining standard deviations of random effects related to the variability between subjects.
在医学研究中使用患者所引发的伦理问题推动了群体动力学中的药代动力学研究，该研究仅需要每个个体的少量血药浓度样本。利用马普替林的历史数据，对群体动力学的新方法进行了研究，并与个体估计动力学进行了比较。应用了两种不同的群体动力学方法。将简单方法（一种快速且粗糙的方法）与由NONMEM软件包应用的非线性混合效应方法进行了比较。基于我们从实际马普替林数据以及模拟数据中获得的结果，NONMEM是估计群体药代动力学参数的合理工具。NONMEM相对于简单方法的主要优势在于能够获得与个体间变异性相关的随机效应的标准差。
