摘要
目的:基于真值及模拟数据,评价不同非房室模型AUC计算方法的准确度和精密度,为AUC算法优选提供依据。方法:使用3种方法计算G药等效试验中0~t曲线下面积(AUC0-t):(1)线性梯形法(Linear法);(2)线性对数梯形法(Linear/Log法):血药浓度最大值(Cmax)之前数据用线性梯形法则计算,Cmax之后用对数梯形法则计算;(3)上升段线性下降段对数法(Linear Up/Log Down法):药-时曲线上升段用线性梯形法则计算,下降段用对数梯形法则计算。并对对数转化后的AUC0-t进行等效性分析,等效标准为80.0%-125.0%。通过模拟数据,比较三种方法差异。结果:24位受试者服用两种制剂的G药后,使用不同AUC0-t计算方法结果不同,等效性分析结论也不全相同,其中使用Linear法和Linear Up/Log Down法得到等效结论,Linear/Log法为不等效。三种方法计算小样本模拟数据,所得AUC0-t差异较大,计算大样本数据,差异较小。结论:Linear/log法在实际工作中应用较少,口服给药及多峰曲线使用Linear Up/Log Down法更合理,小样本量试验或预实验中Linear计算简单,结果稳定。此外应根据分析计划中已制定的AUC计算方法进行计算和生物等效性分析。
AIM:To study the ways of calculating area under the plasma concentration-time curve(AUC)in non-compartment model pharmacokinetics by comparing the accuracy&precision of every method.METHODS:Three methods were used to calculate the area under 0-T curve(AUC0-t)in G drug equivalence test.(1)Linear method(2)Linear/Log method:Data before the maximum blood concentration(Cmax)was calculated by the linear trapezoid rule,and those after Cmaxby logarithmic trapezoid rule(3)Linear Up/Log Down:The ascending part of the curve was calculated by the linear trapezoid rule,and the descending part by logarithmic trapezoid.Equivalence criterion of AUC0-t after logarithmic transformation is 80.0%-125.0%,and differences between three methods were compared on simulated data.RESULTS:Both the AUC0-t and equivalence analysis results show difference between three methods,in these 24 subjects took G drug of two preparations.Furthermore,Linear and Linear Up/Log Down method have the equivalent conclusion,while not the Linear/Log method.AUC0-t showed great difference in small sample of simulation data,contrast to slight difference in the large sample data case.CONCLUSION:Linear Up/Log Down method is more appropriate for oral administration and multi-peak curves,and Linear calculation is more effective to get stable results in small sample size test or pre-test,while Linear/log method is not so often used.In addition,bioequivalence research should be included in AUC calculation in the analysis plan.
作者
陈潮
郑青山
李禄金
李雪
许羚
CHEN Chao;ZHENG Qingshan;LI Lujin;LI Xue;XU Ling(National Drug Clinical Trial Institution of Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2020年第12期1381-1387,共7页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
十三五“重大新药创制”科技重大专项(2017ZX09304001)
国家自然科学基金青年基金项目(81803825)。
作者简介
陈潮,女,硕士研究生,药师,研究方向:临床药理学。Tel:021-64385700-9707,E-mail:cdinglingmiao@163.com;通信作者:许羚,女,博士研究生,助理研究员,研究方向:临床药理、定量药理。Tel:021-51322556,E-mail:xuling_abc@126.com。
