霉酚酸钠肠溶片用于国人肾移植受者的药代动力学监测

Pharmacokinetics monitoring of EC-MPS in Chinese renal allograft recipients

目的：观察服用霉酚酸钠肠溶片（ EC-MPS）的国人肾移植受者血中霉酚酸（ MPA）的药代动力学特征，建立简化的MPA血浆浓度—时间曲线下面积（AUC）的计算公式。方法30例肾移植受者均接受EC-MPS1．44 g／d联合环孢素、强的松的三联免疫抑制方案。采用EMIT法测服药前及服药后0．5、1、1．5、2、4、6、8、10、12 h的血浆MPA浓度（分别为C0．5、C1、C1．5、C2、C4、C6、C8、C10、C12）。采用药理学专用软件计算MPA AUC0～12 h ，并以多元逐步回归分析法得出适合国人的MPAAUC0～12h的简化计算公式。结果30例肾移植受者EC-MPS的药代动力学参数存在显著个体差异。 MPA AUC0～12 h平均值为（47．64±25．14）mg·h／L。选取2个取样时点的C1．5、C2和4个取样时点的C2、C4、C6、C8，分别得出MPA AUC的简化计算公式：AUC＝27．41＋0．87×C1．5＋0．88×C2（r2＝0．67）和AUC＝3．98＋2．03×C2＋2．18×C4＋1．91×C6＋5．08×C8（r2＝0．86），其对MPA AUC预测值的绝对误差分别为（28．8±24．8）％和（12．8±10．1）％；30例肾移植受者中，MPA AUC预测值误差均在MPA AUC0～12 h的＆#177;15％以内。结论服用EC-MPS的国人肾移植受者血浆中MPA药代动力学呈现较大的个体差异；得出取样点少（2个取样时点或4个取样时点）、预测效果好的MPA AUC简化计算公式。

Objective To observe the pharmacokinetics features of mycophenolic acid （ MPA） in Chinese renal al-lograft recipients who took Myfortic （ EC-MPS） and to establish a calculation for the abbreviated MPA area under the curve （AUC） of plasma concentration and time .Methods Thirty renal-transplant recipients were treated with EC-MPS （1.44 g/d） in combination with cyclosporine （ CsA） and prednisone （ Pred） .Plasma MPA concentrations were determined by E-MIT method at pre-medication, 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 hours （C0.5,C1,C1.5,C2,C4,C6,C8,C10 and C12） af-ter oral administration .The MPA AUC0-12 h were calculated by using the trapezoidal rule and the abbreviated MPA AUC model equation fitted to 30 MPA AUC0-12 h profiles was generated by the multiple regression analysis .Results The phar-macokinetics of EC-MPS in 30 renal-transplant recipients manifested great inter-patient difference . The mean MPA AUC0-12 h was （47.64 ±25.14） mg· h/L.We selected C1.5, and C2 at two different time points and C2, C4, C6 and C8 at four different time points.Then, the abbreviated MPA AUC model equations were recommended：AUC=27.41＋0.87 ×C1.5 ＋0.88 ×C2（r2 =0.67）, or AUC=3.98＋2.03 ×C2 ＋2.18 ×C4 ＋1.91 ×C6 ＋5.08 ×C8（r2 =0.86）;the abso-lute prediction error was （28.8 ±24.8）%and （12.8 ±10.1）%, respectively.In 30 recipients, the absolute prediction error between estimated MPA AUC and full MPAAUC 0-12 h was within ＆#177;15%.Conclusions EC-MPS pharmacokinetics in Chinese renal allograft recipients manifests a substantial inter-individual variability .We get the MPA AUC simplified calcu-lation formula, which needs less sampling point and has good predictive effect .