丹参酚酸B在健康人群个体内暴露程度的生物标志物发现  

Biomarker finding of individual salviol B exposures in healthy subjects

作　　者：黄继汉[1] 王鲲[1] 许羚[1] 何迎春[1] 李禄金[1] 杨娟[1] 盛玉成[1] 郑青山[1] 

机构地区：[1]上海中医药大学药物临床研究中心,上海201203

出　　处：《中国临床药理学与治疗学》2011年第5期510-516,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家科技支撑计划项目(2008BAI51B03);上海市教委重点学科项目(J50303);上海市教委创新项目(10YZ61);上海市高校E研究院项目(E03008)

摘　　要：目的：用有限采样方法（LSS）和图形化评价,建立1-4个时点（时间与浓度）的回归方程,估算丹参酚酸B体内暴露程度参数AUC0-24 h和Cmax,从而为个体化用药提供生物标志物。方法：丹参酚酸B 200、300、400 mg在健康受试者静滴给药,LSS法以7 h内血药浓度数据建模。应用Jackknife法验证模型,绝对误差（APE）、误差均方及图形检测表示评价结果。结果：2-4时点的LSS完全可以作为生物标志物去预测体内暴露程度。Jackknife法验证显示,AUC0-24 h用一个时点,27例数据中有8（29.6%）的绝对误差超过15%,采用2、3、4个时点建模预测的结果较好,27例中所有预测结果的APE均在15%以内;Cmax用一个时点,27例数据中有3（11.1%）的绝对误差超过15%。采用2、3、4个时点建模预测结果也较好,27例中分别有2（7.4%）、2（7.4%）和1（3.7%）例预测结果的APE超过15%。结论：2-4个血药丹参酚酸浓度可作为生物标志物,较准确地预测AUC0-24 h和Cmax,从而方便地指导个体用药。AIM： To set a linear regression model in selecting 1-4 point blood concentrations as biomarkers for predicting AUC0-24 h and Cmax in individual therapy. METHODS： The blood concentrations of salviol B were determined by HPLC-UA and the data within 7 h were used to set model.The reliability and stability of the model was evaluated with the absolute prediction error（APE） by Jackknife method and plotting.RESULTS：A limited sampling model was set with 1-4 point concentrations by the regression model with plotting.One point for prediction of AUC0-24 h showed 15% APE 29.6% in subjects,but two,three or four points could obtain better prediction with less than 15% APE in all subjects.There were the same results in the prediction of Cmax in the subjects.CONCLUSION： Two-four point blood concentrations of salviol B can be taken as biomarkers to predict the AUC0-24 h and Cmax for individual therapy.

关 键 词：丹参酚酸B 模型化 有限采样法 刀切法 生物标志物 

分 类 号：R969.1[医药卫生—药理学]