中国临床药学杂志2026，Vol.35Issue(2)：127-133,7.DOI:10.19577/j.1007-4406.2026.02.005
肾移植术后早期患者体内霉酚酸暴露量监测的优化策略
Optimization strategies for monitoring mycophenolic acid exposure in renal transplant patients
摘要
Abstract
AIM To screen and evaluate fitting models for the estimation of mycophenolic acid(MPA)exposure,specifically area under the drug-time curve(AUC0-12 h),in renal transplant patients during the early post-transplant stage,providing a basis for individualized dosing.METHODS A total of 144 blood samples were collected from 18 renal transplant patients during the early post-transplant period,who were treated with a triple immunosuppressive regimen of enteric-coated mycophenolate sodium(EC-MPS),tacrolimus(TAC)and prednisone.Plasma MPA concentrations at different time points(pre-dose and 1.5,2,4,6,8,10,12 hours post-dose)were measured using a fully automated two-dimensional liquid chromatography(2D-LC/UV)system.The AUC0-12h was calculated using the trapezoidal method.Multivariate linear regression equations for concentration versus AUC0-12 h were established using the optimal subset method with 2 or 3 sampling point schemes.Model selection and validation were performed using leave-one-out cross-validation and bootstrap methods.The Bland-Altman analysis was used to assess the agreement between the estimated and measured AUC0-12h values.RESULTS Among the 18 patients,the median trough concentration(ρ0)of MPA was 0.483 μg·mL-1,the mean peak concentration(ρmax)was(10.269±6.345)μg·mL-1,the median time to peak concentration(Tmax)was 2 hours,and the mean AUC0-12h was(25.156±12.788)μg·h·mL-1.Based on a comprehensive evaluation of the correlation coefficient(r2),mean prediction error(MPE),the proportion of samples with an absolute percentage error(APE)＞15％,and the root mean square error(RMSE),the optimal fitting model for estimating the MPA AUC0-12h was determined as:AUC0-12h=0.900ρ1.5+1.128ρ2+2.226 ρ4+5.753(r2=0.842).The MPE was-5.990％,the RMSE was 62.983％,and the the proportion of samples with APE＞15％was 55.556％.The predicted values showed good correlation and agreement with the measured values,and the prediction model demonstrated good stability.CONCLUSION This study established,an MPA exposure estimation model for renal transplant recipients in Yunnan province for the first time.The model offers the advantage of fewer sampling points and is expected to provide a reference for guiding individualized MPA dosing in clinical renal transplant recipients.关键词
霉酚酸/肾移植/药动学/有限采样法/多元线性回归Key words
mycophenolic acid/renal transplantation/pharmacokinetics/limited sampling method/multivariate linear regression分类
医药卫生引用本文复制引用
任思毅,宋沧桑,胡伟,毛盼盼,王国徽,李兴德..肾移植术后早期患者体内霉酚酸暴露量监测的优化策略[J].中国临床药学杂志,2026,35(2):127-133,7.基金项目
云南省临床药学中心建设项目(昆明市第一人民医院) （昆明市第一人民医院）
云南省卫生健康委员会医学领军人才培养项目(编号L-2018012) （编号L-2018012）
云南省基础研究计划(昆医联合专项)(编号202301AY070001-112) （昆医联合专项）
昆明市卫生科技人才培养项目[编号2022-SW(带头)-32] （带头）
