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目的:研究肾移植患者麦考酚酸体内药动学过程,并建立有限采样法估算AUC_(0-12)的模型。方法:建立HPLC法测定人血浆中麦考酚酸的方法。考察9例肾移植患者服用麦考酚酸酯500 mg,bid,达稳态后测定服药前和服药后0.5,1,1.5,2,3,4,6,8,10,12 h的麦考酚酸浓度,用DAS1.0软件拟合药动学过程,并用SPSS软件采用多元线性回归分别拟合单个或2～4个采血点拟合有限采样法估算麦考酚酸AUC_(0-12)的回归方程及相关系数。结果:采用本文建立的方法对多点血药浓度进行测定,主要药动学参数为C_(max)(24.31±17.79)μg·ml~(-1),t_(max)(0.56±0.17)h,AUC_(0-12)(30.82±11.63)μg·h·ml~(-1)。有限采样法拟合AUC_(0-12),其中0.5,1.5,6 h和0.5,1,6 h 3点拟合的回归方程与实测AUC_(0-12)的相关性较好,其复相关系数分别为0.980 7和0.972 4,两者平均预测误差分别为(0.21±6.06)%、(-11.19～8.78)%和(0.64±7.63)%、(-12.53～13.37)%。结论:麦考酚酸药动学个体差异较大。本文拟合的3点预测麦考酚酸AUC_(0-12)简化计算公式能较好地反映其药-时曲线下面积,适合应用于环孢素与麦考酚酸酯合用的中国肾移植受者的治疗药物监测。
OBJECTIVE: To study the pharmacokinetics of mycophenolic acid in renal transplant recipients and to establish a finite sampling method to estimate the AUC_ (0-12) model. Methods: To establish a HPLC method for the determination of mycophenolic acid in human plasma. To investigate the 9 cases of renal transplant patients taking mycophenolate mifepristone 500 mg, bid, up to steady state before and after taking medication 0.5,1,1.5,2,3,4,6,8,10,12 h McCaw The concentration of phenolic acids was fitted to the pharmacokinetics using DAS 1.0 software, and SPSS software was used to fit a single or two to four sampling points to fit the finite sampling method to estimate the mycophenolic acid AUC_ (0-12) Regression equation and correlation coefficient. Results: The multi-point plasma concentration was determined by the method of this article. The main pharmacokinetic parameters were C max (24.31 ± 17.79) μg · ml -1, t max (0.56 ± 0.17) h , AUC 0-12 (30.82 ± 11.63) μg · h · ml -1. The finite sampling method fitting AUC_ (0-12), 0.5,1.5,6 h and 0.5,1,6 h 3 point fitting regression equation and the measured AUC_ (0-12) correlation is good, the complex correlation The coefficients were 0.980 7 and 0.972 4, respectively. The average forecast errors were (0.21 ± 6.06)%, (-11.19 ~ 8.78)% and (0.64 ± 7.63)% and (- 12.53 ~ 13.37)%, respectively. Conclusion: Mycophenolic acid pharmacokinetics vary greatly. The fitting 3-point prediction of mycophenolic acid AUC_ (0-12) simplified calculation formula can better reflect the area under its drug-time curve and is suitable for the combination of cyclosporine and mycophenolate Chinese kidney transplantation Recipient’s therapeutic drug monitoring.