We address the problem of design optimization for individual and population pharmacokinetic studies. We develop Splus generic functions for pharmacokinetic design optimization: IFIM, a function for individual design optimization similar to the ADAPT II software, and PFIM_OPT, a function for population design optimization which is an extension of the Splus function PFIM for population design evaluation. Both evaluate and optimise designs using the Simplex algorithm. IFIM optimizes the sampling times in continuous intervals of times; PFIM_OPT optimizes either, for a given group structure of the population design, only the sampling times taken in some given continuous intervals or, both the sampling times and the group structure, performing then statistical optimization. A combined variance error model can be supplied with the possibility to include parameters of the error model as parameters to be estimated. The performance of the optimization with the Simplex algorithm is demonstrated with two pharmacokinetic examples: by comparison of the optimized designs to those of the ADAPT II software for IFIM, and to those obtained using a grid search or the Fedorov-Wynn algorithm for PFIM_OPT. The influence of the variance error model on design optimization was investigated. For a given total number of samples, different group structures of a population design are compared, showing their influence on the population design efficiency. The functions IFIM and PFIM_OPT offer new efficient solutions for the increasingly important task of optimization of individual or population pharmacokinetic designs.

中文翻译：

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使用Splus优化个人和总体设计。

我们解决了个人和人群药代动力学研究的设计优化问题。我们开发用于药物动力学设计优化的Splus通用功能：IFIM（类似于ADAPT II软件的单个设计优化功能）和PFIM_OPT（用于群体设计优化的功能），它是Splus功能PFIM的扩展，用于群体设计评估。两者均使用Simplex算法评估和优化设计。IFIM以连续的时间间隔优化采样时间；PFIM_OPT要么针对总体设计的给定组结构优化，要么仅对某些给定的连续时间间隔内的采样时间进行优化，要么对采样时间和组结构进行优化，然后执行统计优化。可以提供组合方差误差模型，该可能性包括将误差模型的参数包括为要估计的参数。通过两个药代动力学实例证明了使用Simplex算法进行优化的性能：通过将优化设计与针对IFIM的ADAPT II软件的优化设计以及与针对PFIM_OPT的网格搜索或Fedorov-Wynn算法获得的优化设计进行比较。研究了方差误差模型对设计优化的影响。对于给定的样本总数，比较了总体设计的不同组结构，显示了它们对总体设计效率的影响。IFIM和PFIM_OPT函数为优化个人或群体药代动力学设计这一日益重要的任务提供了新的有效解决方案。