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

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (5): 510-516.

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

黄继汉, 王鲲, 许羚, 何迎春, 李禄金, 杨娟, 盛玉成, 郑青山

上海中医药大学药物临床研究中心,上海 201203

收稿日期:2011-04-25 修回日期:2011-05-12 发布日期:2011-07-08
通讯作者: 郑青山,男,教授,博导,研究方向:定量药理学和生物统计学。Tel:021-51323006 E-mail:zheng.zqs@gmail.com
作者简介:黄继汉,男,博士,研究方向:临床药理学和定量药理学。Tel:021-51322420 E-mail:whhuangjh@163.com.王鲲,男,博士,副研究员,研究方向:定量药理学。Tel:021-51322420 E-mail:kunwang@139.com
基金资助:
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)

Biomarker finding of individual salviol B exposures in healthy subjects

HUANG Ji-han, WANG Kun, XU Ling, HE Ying-chun, LI Lu-jin, YANG Juan, SHENG Yu-cheng, ZHENG Qing-shan

Center of Drug Clinical Research, Shanghai University of Chinese Medicine, Shanghai 201203, China

Received:2011-04-25 Revised:2011-05-12 Published:2011-07-08

摘要/Abstract

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AUC_{0-24 h}和C_max,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,AUC_{0-24 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;C_max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AUC_{0-24 h}和C_max,从而方便地指导个体用药。

关键词: 丹参酚酸B, 模型化, 有限采样法, 刀切法, 生物标志物

Abstract: AIM: To set a linear regression model in selecting 1-4 point blood concentrations as biomarkers for predicting AUC_{0-24 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 AUC_{0-24 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 C_max in the subjects.CONCLUSION: Two-four point blood concentrations of salviol B can be taken as biomarkers to predict the AUC_{0-24 h} and C_max for individual therapy.

Key words: Salviol B, Modeling, Limited sampling model, Jackknife, Biomarker

中图分类号:

R969.1

黄继汉, 王鲲, 许羚, 何迎春, 李禄金, 杨娟, 盛玉成, 郑青山. 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[J]. 中国临床药理学与治疗学, 2011, 16(5): 510-516.

HUANG Ji-han, WANG Kun, XU Ling, HE Ying-chun, LI Lu-jin, YANG Juan, SHENG Yu-cheng, ZHENG Qing-shan. Biomarker finding of individual salviol B exposures in healthy subjects[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(5): 510-516.

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