应用有限采样法估算头孢克洛在健康志愿者体内暴露程度的药动学参数

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (4): 421-427.

应用有限采样法估算头孢克洛在健康志愿者体内暴露程度的药动学参数

黄晓晖¹, 黄继汉², 王钦¹, 王鲲²

¹安徽医科大学药学院基础与临床药理学教研室,合肥 230032,安徽;
²上海中医药大学药物临床研究中心,上海 201203

收稿日期:2012-02-14 修回日期:2012-03-15 发布日期:2012-04-28
作者简介:黄晓晖,男,博士,副教授,硕士生导师,研究方向:定量药理学和临床药代动力学。Tel: 13855183138 E-mail: mathdrug@sina.com
基金资助:
安徽省优秀青年科技基金(08040106813);上海市教委创新项目 (10YZ61)

Calculating the pharmacokinetic parameters of cefaclor in healthy volunteers using limited sampling model

HUANG Xiao-hui¹, HUANG Ji-han², WANG Qin¹, WANG Kun²

¹Department of Basic and Clinical Pharmacology,School of Pharmacy, Anhui Medical University,Hefei 230032, Anhui, China;
²Center of Drug Clinical Research, Shanghai University of Chinese Medicine, Shanghai 201203, China

Received:2012-02-14 Revised:2012-03-15 Published:2012-04-28

摘要/Abstract

摘要： 目的: 应用有限采样方法(LSS)和图形化评价方法,建立1至4个时点血药浓度和时间时点的回归方程,估算头孢克洛体内暴露程度的药动学参数AUC_0-240min和C_max,为个体化用药提供依据及方法。方法: 健康受试者口服用药头孢克洛 250 mg,应用LSS法对 240 min 内血药浓度数据进行建模,并用Jackknife法验证模型,以绝对预测误差(APE)、误差均方及图形检测评价建模结果。结果: 2至4个时点的LSS法可以准确地预测头孢克洛在体内暴露程度。Jackknife法验证结果显示,AUC_{0-240 min} 用一个时点,48例数据中有23 例(47.9%)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,48例中分别有8(16.7%)、4 (8.3%) 和0例预测结果的APE超过15%。C_max用一个时点,48例数据中有24例 (50.0%)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,48例中分别有8 (16.7%)、7 (14.6%) 和7 (14.6%)例预测结果的APE超过15%。结论: 应用有限采样法,采用2至4个血药头孢克洛浓度即可较准确地预测AUC_{0-240 min}和C_max,从而方便地指导个体用药。

关键词: 头孢克洛, 有限采样法, 刀切法, 数学模型

Abstract: AIM: To set a linear regression model in selecting 1-4 point blood concentrations as biomarkers for predicting AUC_0-240min and C_max in individual therapy. METHODS: The blood concentrations of cefaclor were determined by HPLC and the data within 240 min were used for modeling. 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 established with 1-4 point concentrations by the regression model with plotting. One point for prediction of AUC_0-240min showed 15% APE 47.9% 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: Using limited sampling model, two to four blood concentration points of cefaclor can used to predict the AUC_0-24h and Cmax for individual therapy.

Key words: Cefaclor, Limited sampling model, Jackknife, Mathematical model

中图分类号:

R969

黄晓晖, 黄继汉, 王钦, 王鲲. 应用有限采样法估算头孢克洛在健康志愿者体内暴露程度的药动学参数[J]. 中国临床药理学与治疗学, 2012, 17(4): 421-427.

HUANG Xiao-hui¹, HUANG Ji-han², WANG Qin¹, WANG Kun². Calculating the pharmacokinetic parameters of cefaclor in healthy volunteers using limited sampling model[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(4): 421-427.

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