EXPERIMENTAL-DESIGN AND EFFICIENT PARAMETER-ESTIMATION IN POPULATION PHARMACOKINETICS
EXPERIMENTAL-DESIGN AND EFFICIENT PARAMETER-ESTIMATION IN POPULATION PHARMACOKINETICS
复制标题
DOI：
10.1007/bf01062273
复制
发表时间：
1990-08-01
期刊：
影响因子：
--
通讯作者：
WHITING, B
中科院分区：
文献类型：
--
作者：
ALBANNA, MK;KELMAN, AW;WHITING, B
描述了一种用于评估抽样设计的几个方面对群体药代动力学参数估计效率的影响的计算机模拟技术。虽然模拟仅限于一室一指数模型，但它们为设计群体研究所涉及的结构方面的讨论提供了基础。这些方面包括所需的受试者数量、每例受试者的样本数量和这些样本的采集时间。根据两点和三点设计从不同抽样方案获得的参数估计值的准确度和精密度进行了评价。这些模拟数据集包括个体间和个体内变异性的噪声项。结果表明，人口固定效应参数（平均清除率和平均分布容积），这个简单的药代动力学模型有效地估计大多数的采样时间表时，两个或三个点，但随机效应参数（描述间和个体内变异性）是不准确和不精确的采样时间表时，只有两个点使用。通过将每个人的数据点数量增加到三个来弥补这一缺陷。
A computer simulation technique used to evaluate the influence of several aspects of sampling designs on the efficiency of population pharmacokinetic parameter estimation is described. Although the simulations are restricted to the one-compartment one-exponential model, they provide the basis for a discussion of the structural aspects involved in designing a population study. These aspects include number of subjects required, number of samples per subject, and timing of these samples. Parameter estimates obtained from different sampling schedules based on two- and three-point designs are evaluated in terms of accuracy and precision. These simulated data sets include noise terms for both inter- and intraindividual variability. The results show that the population fixed-effect parameters (mean clearance and mean volume of distribution) for this simple pharmacokinetic model are efficiently estimated for most of the sampling schedules when two or three points are used, but the random-effect parameters (describing inter- and intraindividual variability) are inaccurate and imprecise for most of the sampling schedules when only two points are used. This drawback was remedied by increasing the number of data points per individual to three.