Nakai K, Fujita M, Tomita M
Department of Physiological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Int J Clin Pharmacol Ther. 2002 Sep;40(9):431-8. doi: 10.5414/cpp40431.
We investigated the comparison of average bioequivalence approach and population approach using bioequivalence study data which have been reported.
On MEDLINE, "bioequivalence" was entered as a key word to search in the 3 journals which were published between 1980 and 1989. Consequently, a total of 17 data sets on AUC and 12 data sets on Cmax were obtained and analyzed in this review.
Assessment of average bioequivalence, assessment of population bioequivalence and assessment of inequality of variance (F-test) were conducted after all data were subjected to logarithmic conversion.
Of the data sets which were analyzed in this review, 11 data sets on AUC and 3 data sets on Cmax passed the average bioequivalence criterion, and 13 data sets on AUC and 8 data sets on Cmax passed the population bioequivalence criterion. Two data sets on AUC and 1 data set on Cmax passed the average bioequivalence criterion, but not the population bioequivalence criterion. Four data sets on AUC and 6 data sets on Cmax passed the population bioequivalence criterion, but not the average bioequivalence criterion. The correlation coefficient (r) for the population bioequivalence value and difference in the average bioavailability was 0.412, while the correlation coefficient for the population bioequivalence value and the difference in bioavailability variances was 0.708.
In this review using bioequivalence study papers which have been reported in references, the episodes to judge that the test formulation is bioequivalent to the reference formulation occurred more predominantly in the population bioequivalence approach than in the average bioequivalence approach, and population bioequivalence approach might be affected more extensively by the bioavailability variance rather than by the average bioavailability.
我们使用已报道的生物等效性研究数据，对平均生物等效性方法和群体方法进行了比较研究。
在MEDLINE数据库中，以“生物等效性”作为关键词，检索1980年至1989年期间发表的3种期刊。因此，本综述共获得并分析了17个关于AUC的数据集和12个关于Cmax的数据集。
在对所有数据进行对数转换后，进行平均生物等效性评估、群体生物等效性评估和方差不等式评估（F检验）。
在本综述分析的数据集中，11个关于AUC的数据集和3个关于Cmax的数据集通过了平均生物等效性标准，13个关于AUC的数据集和8个关于Cmax的数据集通过了群体生物等效性标准。2个关于AUC的数据集和1个关于Cmax的数据集通过了平均生物等效性标准，但未通过群体生物等效性标准。4个关于AUC的数据集和6个关于Cmax的数据集通过了群体生物等效性标准，但未通过平均生物等效性标准。群体生物等效性值与平均生物利用度差异的相关系数（r）为0.412，而群体生物等效性值与生物利用度方差差异的相关系数为0.708。
在本综述中，使用参考文献中已报道的生物等效性研究论文，判断试验制剂与参比制剂生物等效的情况在群体生物等效性方法中比在平均生物等效性方法中更为普遍，并且群体生物等效性方法可能受生物利用度方差的影响比受平均生物利用度的影响更大。
