CAJ | 학술논문

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±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。
목적：관찰복용매분산납장용편（ EC-MPS）적국인신이식수자혈중매분산（ MPA）적약대동역학특정，건립간화적MPA혈장농도—시간곡선하면적（AUC）적계산공식。방법30례신이식수자균접수EC-MPS1．44 g／d연합배포소、강적송적삼련면역억제방안。채용EMIT법측복약전급복약후0．5、1、1．5、2、4、6、8、10、12 h적혈장MPA농도（분별위C0．5、C1、C1．5、C2、C4、C6、C8、C10、C12）。채용약이학전용연건계산MPA AUC0～12 h ，병이다원축보회귀분석법득출괄합국인적MPAAUC0～12h적간화계산공식。결과30례신이식수자EC-MPS적약대동역학삼수존재현저개체차이。 MPA AUC0～12 h평균치위（47．64±25．14）mg· h／L。선취2개취양시점적C1．5、C2화4개취양시점적C2、C4、C6、C8，분별득출MPA AUC적간화계산공식：AUC＝27．41＋0．87×C1．5＋0．88×C2（r2＝0．67）화AUC＝3．98＋2．03×C2＋2．18×C4＋1．91×C6＋5．08×C8（r2＝0．86），기대MPA AUC예측치적절대오차분별위（28．8±24．8）％화（12．8±10．1）％；30례신이식수자중，MPA AUC예측치오차균재MPA AUC0～12 h적±15％이내。결론복용EC-MPS적국인신이식수자혈장중MPA약대동역학정현교대적개체차이；득출취양점소（2개취양시점혹4개취양시점）、예측효과호적MPA AUC간화계산공식。
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 ±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 .