Mahmood I, Miller R
Division of Pharmaceutical Evaluation I, Office of Clinical Pharmacology and Biopharmaceutics, Rockville, MD 20852, USA.
Int J Clin Pharmacol Ther. 1999 Sep;37(9):439-45.
To compare two limited sampling methods (Bayesian and the limited sampling model) for the estimation of AUC and Cmax following a single oral dose of a hypothetical drug.
The plasma concentration vs time data sets for 50 subjects using a linear one- or two-compartment pharmacokinetic model were generated by simulation. The limited sampling model (LSM) was developed using samples from 10 subjects using one or two time points. The simulated plasma concentrations were also used for Bayesian evaluation. Bayesian analysis was performed on Non-Mem and mean pharmacokinetic parameters used for simulation were assumed as population pharmacokinetic parameters. In addition a test drug was also used to compare the predicted AUC and Cmax for the two approaches.
Both methods were validated in 40 subjects for the hypothetical drug and in 12 subjects for the test drug. Both methods provided good estimates of AUC and Cmax.
The results indicate that the LSM is similar to the Bayesian method and may be used in lieu of the Bayesian approach in estimating AUC and Cmax using one or two samples in clinical settings without detailed pharmacokinetic studies.
比较两种有限采样方法（贝叶斯法和有限采样模型）在单次口服一种假设药物后估算曲线下面积（AUC）和最大血药浓度（Cmax）的效果。
采用线性一室或二室药代动力学模型，通过模拟生成50名受试者的血药浓度-时间数据集。有限采样模型（LSM）利用10名受试者的一个或两个时间点的样本建立。模拟的血药浓度也用于贝叶斯评估。在Non-Mem软件上进行贝叶斯分析，并将用于模拟的平均药代动力学参数假定为群体药代动力学参数。此外，还使用一种受试药物比较两种方法预测的AUC和Cmax。
两种方法在40名使用假设药物的受试者和12名使用受试药物的受试者中均得到验证。两种方法对AUC和Cmax的估算效果均良好。
结果表明，有限采样模型与贝叶斯方法相似，在临床环境中，无需进行详细的药代动力学研究，使用一两个样本估算AUC和Cmax时，有限采样模型可替代贝叶斯方法。
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