Nedelman J R, Gibiansky E, Lau D T
Department of Clinical Pharmacology, Sandoz Research Institute, Sandoz Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA.
Pharm Res. 1995 Jan;12(1):124-8. doi: 10.1023/a:1016255124336.
Bailer developed a method for constructing confidence intervals for areas under the concentration-vs-time curve (AUC's) with only one sample per subject but with multiple subjects sampled at each of several time points post dose. We have modified this method to account for estimation of the variances. How the need to estimate variances affects study design is discussed. An extension of Bailer's method is proposed where variances are modeled as a function of the means, in order to get more precise estimates of variances. The modified and extended methods are applied to a rat toxicokinetic study with only two rats per time point per treatment group.
贝勒开发了一种方法，用于构建浓度-时间曲线下面积（AUC）的置信区间，每个受试者仅取一个样本，但在给药后的几个时间点对多个受试者进行采样。我们对该方法进行了修改，以考虑方差的估计。讨论了估计方差的需求如何影响研究设计。提出了贝勒方法的一种扩展，将方差建模为均值的函数，以便获得更精确的方差估计。将修改后的方法和扩展后的方法应用于一个大鼠毒代动力学研究，每个治疗组每个时间点仅用两只大鼠。
