肾移植术后早期患者体内霉酚酸暴露量监测的优化策略OA

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.