造血干细胞移植患者霉酚酸药-时曲线下面积有限采样模型的应用研究  

Application of Limited Sampling Strategy Model for the Area Under the Concentration-Time Curve of Mycophenolic Acid in Hematopoietic Stem Cell Transplantation Recipients

作　　者：林良沫[1] 洪绵慧 符祥俊[2] LIN Liangmo;HONG Mianhui;FU Xiangjun(Dept.of Pharmacy,Hainan General Hospital/Affiliated Hospital of Hainan Medical University,Haikou 570311,China;Dept.of Hematology,Hainan General Hospital/Affiliated Hospital of Hainan Medical University,Haikou 570311,China)

机构地区：[1]海南省人民医院/海南医科大学附属海南医院药学部,海口570311 [2]海南省人民医院/海南医科大学附属海南医院血液内科,海口570311

出　　处：《中国医院用药评价与分析》2024年第11期1333-1335,1339,共4页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：海南省自然科学基金资助项目(No.822QN452)。

摘　　要：目的:对造血干细胞移植(HSCT)患者展开霉酚酸药-时曲线下面积(MPA-AUC)有限采样(LSS)模型的应用研究,为临床合理评估霉酚酸药物暴露提供参考。方法:以2022年4月至2024年3月于该院接受异基因HSCT的患者为研究对象,在服用吗替麦考酚酯的第8日进行密集采样,收集并监测服药前至服药后12 h期间的8个采样点MPA血浆浓度,使用梯形法计算MPA-AUC。同时采用已发表的LSS模型预测上述患者的MPA-AUC结果,将两组结果进行比较以评估该LSS模型的预测能力。结果:共纳入患者25例,收集MPA血浆浓度200份。入组患者采用梯形法计算的MPA-AUC_(0~12 h)平均值为(16.33±4.10)mg·h/L(8.28~25.25 mg·h/L),采用LSS模型计算的MPA-AUC_(0~12 h)平均值为(16.15±4.17)mg·h/L(9.28~27.59 mg·h/L),两者的差异无统计学意义(P>0.05)。多因素分析提示,除MMF服药后12 h的血浆浓度外,其余各时间点的血浆浓度与AUC的相关性低。模型的绝对预测偏差(APE)为(2.44±1.56)mg·h/L,APE%<20%。结论:本研究的LSS模型具有较好的预测性能,可用于该院HSCT患者MPA的治疗药物监测,是评估MPA药物暴露的良好方法。OBJECTIVE:To perform limited sampling strategy(LSS)model for the area under the concentration-time curve of mycophenolic acid(MPA-AUC)in hematopoietic stem cell transplantation recipients(HSCT),so as to provide reference for rational clinical evaluation of drug exposure for mycophenolic acid.METHODS:Patients who received allogeneic HSCT at the hospital from Apr.2022 to Mar.2024 were enrolled.Intensive sampling was performed on the 8 th day of mycophenolate mofetil administration.MPA plasma concentrations at 8 sampling points from before administration to after administration of 12 h were collected and monitored.MPA-AUC was calculated by using trapezoidal method.The published LSS model was used to predict MPA-AUC outcomes in these patients,and the two sets of results were compared to evaluate the predictive ability of the LSS model.RESULTS:A total of 25 patients were included and 200 MPA plasma concentrations were collected.The average MPA-AUC_(0-12 h) calculated by trapezoidal method was(16.33±4.10)mg·h/L(from 8.28 to 25.25 mg·h/L).The average MPA-AUC_(0-12 h) calculated by LSS model was(16.15±4.17)mg·h/L(from 9.28 to 27.59 mg·h/L),and there was no significant difference between two methods(P>0.05).Multivariate analysis indicated that the correlation between plasma concentration and AUC was low at all time points except for the plasma concentration at 12 h after MMF administration.The absolute prediction deviation(APE)of the model wass(2.44±1.56)mg·h/L,with APE%<20%.CONCLUSIONS:The LSS model in this study has acceptable predictive performance,which can be used for the therapeutic drug monitoring of MPA in HSCT in the hospital,and is a good method to evaluate the drug exposure of MPA.

关 键 词：霉酚酸 药-时曲线下面积 有限采样模型 造血干细胞移植 

分 类 号：R979.5[医药卫生—药品]