Bois F Y, Tozer T N, Hauck W W, Chen M L, Patnaik R, Williams R L
Indoor Environment Program, Lawrence Berkeley Laboratory, Berkeley, California 94720.
Pharm Res. 1994 May;11(5):715-22. doi: 10.1023/a:1018932430733.
The determination of the area under the concentration-time curve (AUC) is the method most commonly used by regulatory agencies to assess extent of drug absorption after single-dose administration of oral products. Using simulations, several approaches toward measuring the actual area, in whole or part, were tested. In addition, the performance of the peak concentration (Cmax), usually taken as a measure of the rate of absorption was assessed evaluating extent. Model scenarios for drugs with typical mean characteristics and statistical distributions were investigated. Using different kinetic models of disposition, the time course of the drug concentration in plasma was simulated. Intraindividual and interindividual variability and assay error were modeled using Monte Carlo techniques. The accuracy, precision, and ease of use of the various measures of extent were evaluated, and statistical power analyses were performed. Among the measures tested, the most reliable were the AUC computed up to the time of the last quantifiable concentration, without extrapolation, and Cmax. However, being also sensitive to rate, Cmax as a measure of extent is of limited potential.
浓度-时间曲线下面积（AUC）的测定是监管机构评估口服产品单剂量给药后药物吸收程度最常用的方法。通过模拟，测试了几种测量全部或部分实际面积的方法。此外，评估峰浓度（Cmax）（通常作为吸收速率的指标）时，对其吸收程度进行了评估。研究了具有典型平均特征和统计分布的药物的模型场景。使用不同的处置动力学模型，模拟了血浆中药物浓度的时间过程。使用蒙特卡罗技术对个体内和个体间变异性以及分析误差进行建模。评估了各种吸收程度测量方法的准确性、精密度和易用性，并进行了统计功效分析。在所测试的测量方法中，最可靠的是在不进行外推的情况下计算至最后可量化浓度时间的AUC以及Cmax。然而，由于Cmax对速率也敏感，作为吸收程度的指标，其潜力有限。
