Zintzaras E, Bouka P, Kowald A
National Agricultural Research Foundation, Athens, Greece.
Eur J Drug Metab Pharmacokinet. 2002 Jan-Mar;27(1):11-6. doi: 10.1007/BF03190400.
Bioequivalence of two medicinal, or veterinary, products is established by comparing the mean of bioavailability measures, such as AUC and Cmax, following administration of the test (T) and reference (R) products. However, the use of these parameters has several drawbacks, e.g. they do not take into consideration the overall pharmacokinetic profile shape. Therefore, concerns have been raised regarding their appropriateness for assessment of bioequivalence. To overcome the limitations of these bioequivalence parameters, direct curve comparison metrics methods were recently proposed on an average basis. In this paper, an individual based direct curve comparison method for assessing bioequivalence is proposed. The bioequivalence of T and R in each subject is evaluated by a new curve comparison metrics delta. The metrics delta is the absolute sum of the difference between two curves. The significance of the metrics for each subject is assessed by bootstrapping. An overall bioequivalence of T and R may be considered if less than 25% of the subjects show statistically different profiles.
通过比较受试产品（T）和参比产品（R）给药后的生物利用度测量值（如AUC和Cmax）的均值，来确定两种药品或兽药的生物等效性。然而，使用这些参数存在几个缺点，例如它们没有考虑整体药代动力学曲线的形状。因此，人们对它们用于评估生物等效性的适用性提出了担忧。为了克服这些生物等效性参数的局限性，最近提出了基于平均的直接曲线比较指标方法。本文提出了一种基于个体的直接曲线比较方法来评估生物等效性。通过一种新的曲线比较指标delta来评估每个受试者中T和R的生物等效性。指标delta是两条曲线之间差异的绝对值之和。通过自抽样法评估每个受试者指标的显著性。如果少于25%的受试者显示出统计学上不同的曲线，则可认为T和R具有整体生物等效性。
