Because bioequivalence studies are performed using a crossover design, information on the intra-subject coefficient of variation (intra-CV) for pharmacokinetic measures is needed when determining the sample size. However, calculated intra-CVs based on bioequivalence results of identical generic drugs produce different estimates. In this study, we collected bioequivalence results using public resources from the Ministry of Food and Drug Safety (MFDS) and calculated the intra-CVs of various generics. For the generics with multiple bioequivalence results, pooled intra-CVs were calculated. The estimated intra-CVs of 142 bioequivalence studies were 14.7±8.2% for AUC and 21.7±8.8% for Cmax. Intra-CVs of Cmax were larger than those of area under the concentration-time curve (AUC) in 129 studies (90.8%). For the 26 generics with multiple bioequivalence results, the coefficients of variation of intra-CVs between identical generics (mean±sd (min ~ max)) were 38.0±24.4% (1.9 ~ 105.3%) for AUC and 27.9±18.2% (4.0 ~ 70.1%) for Cmax. These results suggest that substantial variation exists among the bioequivalence results of identical generics. In this study, we presented the intra-CVs of various generics with their pooled intra-CVs. The estimated intra-CVs calculated in this study will provide useful information for planning future bioequivalence studies. (This is republication of the article 'Transl Clin Pharmacol 2017;25:179-182' retracted from critical typographic errors. See the 'Retraction and Republication section of this issue for further information).

中文翻译：

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对药代动力学指标的受试者内变异系数进行事后分析，以计算生物等效性研究的最佳样本量。


由于生物等效性研究是使用交叉设计进行的，因此在确定样本量时需要有关药代动力学测量的受试者内变异系数 (intra-CV) 的信息。然而，根据相同仿制药的生物等效性结果计算的内部 CV 会产生不同的估计值。在本研究中，我们利用食品药品安全部 (MFDS​​) 的公共资源收集了生物等效性结果，并计算了各种仿制药的内部 CV。对于具有多个生物等效性结果的仿制药，计算了汇总的内部CV。 142 项生物等效性研究的估计内部 CV 的 AUC 为 14.7±8.2%，Cmax 为 21.7±8.8%。在 129 项研究中 (90.8%)，Cmax 的内部 CV 大于浓度-时间曲线下面积 (AUC)。对于具有多个生物等效性结果的26个仿制药，相同仿制药之间的CV内变异系数（平均值±标准差（最小值〜最大值））分别为AUC 38.0±24.4％（1.9〜105.3％）和27.9±18.2％（4.0） Cmax 约为 70.1%）。这些结果表明，相同仿制药的生物等效性结果之间存在显着差异。在本研究中，我们展示了各种仿制药的内部 CV 及其汇总的内部 CV。本研究中计算的估计内部 CV 将为规划未来的生物等效性研究提供有用的信息。 （这是文章“Transl Clin Pharmacol 2017;25:179-182”的再版，因严重的印刷错误而被撤回。有关更多信息，请参阅本期的“撤回和再版”部分）。