肾移植术后早期血麦考酚酸浓度-时间曲线下面积的有限取样法  

A limited sampling strategy for the estimation of total mycophenolic acid early after renal transplantation

作　　者：蔡文娥[1] 覃音红[1] 孙煦勇[1] 秦科[1] 董建辉[1] 吴风富[1] 叶常青[1] 赵东海[1] 周洁慧[1] 李海滨[1] 谭落娇 

机构地区：[1]解放军第三○三医院移植医学研究院广西移植医学重点实验室广州军区器官移植中心,南宁530021 [2]总参管理保障部北极寺老干部服务局门诊部

出　　处：《中华器官移植杂志》2014年第12期719-723,共5页Chinese Journal of Organ Transplantation

基　　金：广西自然基金项目（2013gxnsfaa019253）;广西卫生厅自筹经费科研项目（Z2011011）;广西卫生厅白筹经费科研项目（Z2012464）

摘　　要：目的采用酶标放大免疫技术检测成人肾移植受者术后早期使用吗替麦考酚酯（MMF）后血麦考酚酸（MPA）的药代动力学特点，应用有限取样法确定血MPA药浓度一时间曲线下面积（MPAAUC）的拟合方程。方法67例受者均采用MMF配伍他克莫司和泼尼松的基础免疫抑制方案。术后7d根据内生肌酐清除率（CrCl）将受者分为A组（CrCl≥50ml／min），B组（30ml／min≤CrCl〈50ml／min）和C组（CrCl〈30ml／min），采集受者服药前（0h）、服药后0．5h、1h、1．5h、2h、4h、6h、8h、10h、12h的外周血样本，分析各组MPA药代动力学参数，并通过多元线性回归分析确定有限取样方案。结果C组AUCO0-12h与A组有显著差异（P〈0．05），A组和B组间药动学参数差异无统计学意义（P〉0．05）。A组＋B组＋C组（ABC组）4点拟合方程为MPAAUC0-12h=4．102＋4．514C6h＋1．893C2h＋4．278C10h＋0．828C0．5h（调整r^2=0．906）；A组＋B组（AB组）4点拟合方程为MPAAUC0-12h=12．883＋1．402C2h＋1．552C6h＋2．958C8h＋1．295C4h（调整r^2=0．819），C组3点拟合方程为MPAAUC0-12h=7．888＋1．957C1.5h＋5．568C6h＋2．246C12h（调整r^2=0．931），4点拟合方程为AUC0-12h=4．129＋1．511C1.5h＋5．796C6h＋2．375C12h＋1．074C1h（调整r^2=0．957）；估算误差、精确度、精密度均在临床可接受范围。AB组3点拟合方程MPAAUC0-12h=14．925＋1．487C2h＋2．946C6h＋2．659C8h及C组2点拟合方程MPAAUC0-12h=9．222＋1．910C1.5h＋6．709C6n的误差指数接近临床可接受范围。结论根据肾移植术后移植肾功能恢复的情况，选取合适的取样点，可以得到比较精确的MPAAUC0-12h拟合方程，使取样方案更便捷、经济和灵活。Objective To investigate the pharmacokinetics of mycophenolate mofetil （MMF） in adults early after renal transplantation by an enzyme multiplied immunoassay technique （EMIT） and to establish a limited sampling strategy （LSS） to predict the area under the concentration time curve of blood levels of mycophenolic acid （MPA-AUC）. Method Sixty-seven recipients who underwent renal transplantation with an organ donation after cardiac death （DCD） used a triple immunosuppressant strategy of MMF, tacrolimus and prednisone. On the seventh day post-transplantation, blood samples were collected at 0 h （pre-dose） and at 0. 5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h post-dose （C4）h, C9.5h, C1h, C1.5h, C2h, C4h, C6h, C4h, C10h and C12h, respectively）. EMIT was used to measure mycophenolic acid concentration, According to the creatinine clearance （CrC1） , the 67 recipients were divided into group A （ CrCl≥50 mL/min）, group B （30 mL/min≤CrCl〈50 mL/min） and group C （CrCl〈30 mL/min）. Model equations were generated by multiple stepwise regression analysis to determine MPA-AUC0-12h. Result There was significant difference in AUC0-12hbetween group A and group C （P〈 0. 05 ）. The other pharmacokinetic parameters among groups had no statistically significantdifference （P〉0. 05）. The four point equation obtained by multiple linear regression analysis in the A ＋ B＋ C group was MPA AUC0-12h = 4. 102 ＋ 4. 514C6h ＋ 1. 893C3h ＋ 4. 278C10h ＋ 0. 828C0.5h （adjusted r^2 = 0. 906）, and that in A＋ B group was MPA-AUC0-12h = 12. 883 ＋ 1. 402C2h ＋ 1. 552C6h ＋ 2. 958C8h ＋ 1. 295C4h （adjusted r^2 = 0. 819）. In addition, the three point equation in group C was MPA-AUC0-12h = 7. 888 ＋ 1. 957C1.5h ＋ 5. 568C6h ＋ 2. 246C12h （adiusted r^2 = 0. 931） and four point equation was MPA- AUC0-12h = 4. 129 ＋ 1. 511C1. 5h ＋ 5. 796C6h ＋ 2. 375C12h ＋ 1. 074 C1h （adjusted r^2 = 0. 957）. The bias, accuracy, and precision of the prediction formula were clinically ac

关 键 词：肾移植 麦考酚酸 有限取样 

分 类 号：R699.2[医药卫生—泌尿科学]