CAJ | 학술논문

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-时间曲线下面积(MPA AUC)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≥50 ml/min),B组(30 ml/min≤CrCl＜50 ml/min)和C组(CrCl＜30 ml/min),采集受者服药前(0 h)、服药后0.5h、1h、1.5h、2h、4h、6h、8h、10 h、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AUC0～12h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MPA AUC0～12 h =4.102+4.514C6 h+1.893C2 h+4.278 C10h+0.828 C0.5 h(调整r2=0.906);A组+B组(AB组)4点拟合方程为MPA AUC0～12 h=12.883+1.402 C2 h+1.552 C6 h+2.958 C8 h+1.295 C4 h(调整r2 =0.819),C组3点拟合方程为MPA AUC0～12 h=7.888+ 1.957 C1.5 h+5.568 C6 h+2.246 C12 h(调整r2=0.931),4点拟合方程为AUC0～12 h =4.129+1.511 C1.5 h+5.796 C6 h+2.375 C12 h+1.074 C1 h(调整r2=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MPA AUC0～12h =14.925+1.487 C2 h+2.946 C6 h+2.659 C8h及C组2点拟合方程MPA AUC0～12 h=9.222+1.910C1.5h +6.709 C6h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MPA AUG～12h拟合方程,使取样方案更便捷、经济和灵活.
목적 채용매표방대면역기술검측성인신이식수자술후조기사용마체맥고분지(MMF)후혈맥고분산(MPA)적약대동역학특점,응용유한취양법학정혈MPA약농도-시간곡선하면적(MPA AUC)적의합방정.방법 67례수자균채용MMF배오타극막사화발니송적기출면역억제방안.술후7d근거내생기항청제솔(CrCl)장수자분위A조(CrCl≥50 ml/min),B조(30 ml/min≤CrCl＜50 ml/min)화C조(CrCl＜30 ml/min),채집수자복약전(0 h)、복약후0.5h、1h、1.5h、2h、4h、6h、8h、10 h、12h적외주혈양본,분석각조MPA약대동역학삼수,병통과다원선성회귀분석학정유한취양방안.결과 C조AUC0～12h여A조유현저차이(P＜0.05),A조화B조간약동학삼수차이무통계학의의(P＞0.05).A조+B조+C조(ABC조)4점의합방정위MPA AUC0～12 h =4.102+4.514C6 h+1.893C2 h+4.278 C10h+0.828 C0.5 h(조정r2=0.906);A조+B조(AB조)4점의합방정위MPA AUC0～12 h=12.883+1.402 C2 h+1.552 C6 h+2.958 C8 h+1.295 C4 h(조정r2 =0.819),C조3점의합방정위MPA AUC0～12 h=7.888+ 1.957 C1.5 h+5.568 C6 h+2.246 C12 h(조정r2=0.931),4점의합방정위AUC0～12 h =4.129+1.511 C1.5 h+5.796 C6 h+2.375 C12 h+1.074 C1 h(조정r2=0.957);고산오차、정학도、정밀도균재림상가접수범위.AB조3점의합방정MPA AUC0～12h =14.925+1.487 C2 h+2.946 C6 h+2.659 C8h급C조2점의합방정MPA AUC0～12 h=9.222+1.910C1.5h +6.709 C6h적오차지수접근림상가접수범위.결론 근거신이식술후이식신공능회복적정황,선취합괄적취양점,가이득도비교정학적MPA AUG～12h의합방정,사취양방안경편첩、경제화령활.
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 (C0h,C0.5h,C1h,C1.5h,C2h,C4h,C6h,C8h,C10h and C12h,respectively).EMIT was used to measure mycophenolic acid concentration,According to the creatinine clearance (CrCl),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 significant difference (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 + 1.893C2h + 4.278C10h + 0.828C0.5h (adjusted r2 =0.906),and that in A+ B group was MPA-AUC0-12h =12.883 + 1.402C2h + 1.552C6h + 2.958C8h + 1.295C4h (adjusted r2 =0.819).In addition,the three point equation in group C was MPA-AUC0-12h =7.888 + 1.957C1.5h + 5.568C6h + 2.246C12h (adjusted r2 =0.931) and four point equation was MPAAUC0-12h =4.129 + 1.511C1.5h + 5.7％C6h + 2.375C12h + 1.074 C1h (adjusted r2 =0.957).The bias,accuracy,and precision of the prediction formula were clinically acceptable.Conclusion In adults receiving MMF and tacrolimus early after renal transplantation,different point equation can be chosen to predict MPA-AUC0-12h according to the graft function recovery,which makes the LSS more convenient,economic,flexible.