有限抽样法估算健康志愿者口服环孢素A的药时曲线下面积

Estimation areas under the curve after oral administration cyclosporin A in healthy volunteers by limited sampling strategy

目的 用有限抽样法(LSS)估算健康志愿者口服环孢素A(CsA)微乳制剂药时曲线下面积(AUC)。方法 20名健康志愿者单剂量口服CsA微乳制剂,用高效液相法测定CsA的血药浓度,以LSS建立回归数学模型,用Jacknife法验证回归模型的准确性。结果 单个血药浓度-时间点预测AUC0-12回归模型,线性关系较差;部分2点和3点预测AUC0-12回归模型,线性关系较好(γ2 >0. 9,P<0. 05),其中C2,C6 预测AUC0-12回归模型,线性关系最佳,且准确性好。结论 以LSS法估算口服CsA微乳制剂AUC0-12准确性好,临床上可用于CsA治疗药物监测。

Objective To estimate of cyclosporin A (CsA)microemulsion areas under the curve in 20 Chinese healthy volunteers with a limited sampling strategy(LSS). Methods A single dose of CsA microemulsion was administrated to 20 healthy volunteers.The concentration of CsA in whole blood was determined by validated high performance liquid chromatography (HPLC) method. Multilinear regression analysis were performed to establish a model to estimate AUC of CsA by LSS method. The Jacknife procedure were found to be precise and unbias as compared with reference AUC. Results The linearity relationship between AUC and single concentration point was poor. Several models for CsA AUC estimation met the predefined criteria(γ 2>0.9,P<0.05).The AUC of CsA was best estimated by C 2 and C 6.Conclusion A multilinear regression model for estimation AUC of CsA by using LSS method was developed. The method was accuracy and considered desirable for CsA therapeutic drug monitoring.