基于既往生物等效性研究的药代动力学参数个体内变异的评估  

Assessment of within-subject variance of pharmacokinetic parameters based on previous bioequivalence studies

作　　者：孙华[1] 李相鸿[1] 徐毛迪 梁大虎[1,2] 周理想 谢海棠[1] SUN Hua;LI Xiang-hong;XU Mao-di;LIANG Da-hu;ZHOU Li-xiang;XIE Hai-tang(Center for Drug Clinical Evaluation,Yijishan Hospital Affiliated to Wannan Medical College,Wuhu 241000,Anhui Province,China;School of Pharmacy,Fudan University,Shanghai 201203,China)

机构地区：[1]皖南医学院弋矶山医院药物评价中心,安徽芜湖241000 [2]复旦大学药学院,上海201203

出　　处：《中国临床药理学杂志》2023年第13期1962-1966,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的基于既往研究挖掘与合并药代动力学(PK)参数的个体内变异(CV_(w))信息,以指导生物等效性(BE)研究的样本量设计。方法以吉非替尼片BE研究为例,系统介绍通过双交叉BE研究的置信区间结果计算与合并CV_(w)的原理与方法。提供合并个体内变异系数(Pooled CV_(w))的计算步骤以及SAS的实现。结果可通过既往文献中的置信区间信息对PK参数的CV_(w)进行有效评估,当不同文献来源中所求算的CV_(w)不一致时,可采用Pooled CV_(w)来进行样本量估算。结论基于多项既往研究的Pooled CV_(w)可作为CV_(w)真值的估计。本研究所介绍的方法可应用于既往BE研究中CV_(w)信息的挖掘与汇总,有助于在BE研究前通过文献全面准确了解药物的CV_(w)信息,对BE样本量决策提供参考。Objective To mine the information about within-subject variance from preious bioequivalence studies to guide the design of sample size from previous bioequivalence studies.Methods The principles and methods on how to calculate and pool the within-subject coefficients of variation from the reported confidence interval results were elaborately introduced by the case of bioequivalence study of gefitinib.The calculation steps of pooled within-subject variance coefficient and the implementation by the SAS code were also provided.Results The within-subject variance coefficients of pharmacokinetic paramenters were evaluated by the results of the confidence interval from literature on bioequivalence study.Pooling of within-subject variance coefficients from multiple bioequivalence results could produce more reliable estimate for designing bioequivalence study when the within-subject variance coefficients based on different previous studies varied considerably.Conclusion The pooled within-subject variation coefficient from multiple previous studies can be interpreted as reasonable approximation for the values of the true CV_(w).The calculation method and the SAS code provided in this study can be applied to mine the information about within-subject variance from previous studies and be useful for planning the sample size for future bioequivalence study.

关 键 词：生物等效性 个体内变异系数 合并个体内变异系数 置信区间 样本量估算 

分 类 号：R97[医药卫生—药品]