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  

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

作　　者：黄晓晖[1] 黄继汉[2] 王钦[1] 王鲲[2] 

机构地区：[1]安徽医科大学药学院基础与临床药理学教研室 [2]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》2012年第4期421-427,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省优秀青年科技基金(08040106813);上海市教委创新项目(10YZ61)

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AUC0-240min和Cmax,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250mg,应用LSS法对240min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,AUC0-240min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%。Cmax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AUC0-240min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 AUC0-240min and Cmax 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 AUC0-240min 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 Cmax in the subjects.CONCLUSION： Using limited sampling model,two to four blood concentration points of cefaclor can used to predict the AUC0-24h and Cmax for individual therapy.

关 键 词：头孢克洛 有限采样法 刀切法 数学模型 

分 类 号：R969[医药卫生—药理学]