Zintzaras E
Department of Biomathematics, School of Medicine, University of Thessaly, Larisa, Greece.
Eur J Drug Metab Pharmacokinet. 2005 Jan-Jun;30(1-2):41-6. doi: 10.1007/BF03226406.
A generic drug product (test product) is bioequivalent to an innovator product (reference product) when their bioavailabilities in the same molar dose are similar. Bioavailability is expressed by pharmacokinetic parameters such as the area under plasma concentration-time curve (AUC), the maximum plasma concentration (Cmax) and the time of maximum plasma concentration (tmax). The assessment of bioequivalence is carried out by in vivo bioequivalence studies. This paper examines and appraises design issues for performing a bioequivalence study: the use of crossover, parallel, replicated, and add-on designs; and the determination of sample size. In addition, it presents the valid statistical approaches for proving bioequivalence: average bioequivalence on transformed and untransformed data; parametric and non-parametric analyses; moment based individual bioequivalence; direct curve comparison metrics.
当一种仿制药产品（受试产品）与创新药产品（参比产品）在相同摩尔剂量下的生物利用度相似时，二者具有生物等效性。生物利用度由药代动力学参数表示，如血浆浓度-时间曲线下面积（AUC）、血浆最大浓度（Cmax）和血浆最大浓度出现时间（tmax）。生物等效性评估通过体内生物等效性研究进行。本文审视并评估了开展生物等效性研究的设计问题：交叉、平行、重复和追加设计的使用；以及样本量的确定。此外，还介绍了证明生物等效性的有效统计方法：对转换和未转换数据的平均生物等效性；参数和非参数分析；基于矩的个体生物等效性；直接曲线比较指标。
