有限采样法估算重症感染患者卡泊芬净的药-时曲线下面积  

Estimation of the Area Under the Drug Concentration-Time Curve of Caspofungin in Patients with Severe Infection by Limited Sampling Strategy

作　　者：陈文倩[1] 王晓雪[1] 刘慧芳 杜雯雯[1] 王芊霖 张丹[1] 詹庆元[1] 张相林[1] 李朋梅[1] CHEN Wenqian;WANG Xiaoxue;LIU Huifang;DU Wenwen;WANG Qianlin;ZHANG Dan;ZHAN Qingyuan;ZHANG Xianglin;LI Pengmei(China-Japan Friendship Hospital,Beijing,China 100029)

机构地区：[1]中日友好医院,北京100029

出　　处：《中国药业》2020年第13期9-13,共5页China Pharmaceuticals

基　　金：国家自然科学基金[81870072];国家重点研发计划重大慢性非传染性疾病防控研究重点专项[2016YFC1304300]。

摘　　要：目的建立有限采样法估算重症感染患者卡泊芬净的药-时曲线下面积(AUC)模型。方法重症感染患者静脉输注维持剂量卡泊芬净50 mg,每日1次,输注时间为0.5 h,达稳态后以超高效液相色谱-串联质谱(UPLC-MS/MS)法测定给药前及给药后0.5,1,2,3,5,9,12,24 h时的血浆药物浓度。以梯形面积法计算AUC0-24,采用SPSS 22.0统计学软件,以多元逐步线性回归法建立有限采样模型。结果最终纳入24例患者的血药浓度数据,其AUC0-24为(167.81±46.03)μg/(mL·h);采集2~4个时间点血药浓度方案的回归方程预测能力优于单点采血;其中2个时间点C9,C24,3个时间点C0.5,C9,C24,4个时间点C0.5,C1,C9,C24方案的预测性能良好,调整相关系数(r2)分别为0.962,0.977,0.983;结合预测精准性及可操作性,推荐3点方案方程为7.911+2.606×C0.5+13.765×C9+4.662×C24。结论重症感染患者中卡泊芬净存在药动学差异,以给药后0.5,9,24 h时的卡泊芬净浓度可准确估算AUC0-24,为个体化给药提供基础。Objective To establish a model for estimating the area under the concentration-time curve(AUC)of caspofungin in patients with severe infection by limited sampling strategy.Methods Patients with severe infectionwere administrated with 50 mg caspofunginonce a day,0.5 h for each infusion.The plasma drug concentration before and 0.5,1,2,3,5,9,12,24 h after administration was measured by ultra highperformance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The area under the 0-24 h drug concentration-time curve(AUC0-24)was calculated by trapezoid area method,and the limited sampling model was established by multiple stepwise linear regression method with SPSS22.0 software.Results The plasma concentration data of 24 patients was included.The AUC0-24 was(167.81±46.03)μg/mL·h.The prediction ability of regression equation of 2-4 time points was better than that of single point.Among them,two time points C9,C24,three time points C0.5,C9,C24,and four time point schemes C0.5,C1,C9,C24 had good prediction performance,and the adjusted correlation coefficients r2 were 0.962,0.977 and 0.983 respectively.Combined with the prediction accuracy and operability,it was recommended that the equation of 3-point function was 7.911+2.606·C0.5+13.765·C9+4.662·C24.Conclusion There are obvious pharmacokinetic differences in the patients with severe infection.The therapeutic index AUC0-24 can be accurately estimated by the concentration of caspofungin at 0.5,9 and 24 h after administration,which provides the basis for individualized administration.

关 键 词：有限采样法 卡泊芬净 药-时曲线下面积 重症感染 

分 类 号：R969.4[医药卫生—药理学] R978.1[医药卫生—药学]