Yang Shun-liang, Gao Xia, Wang Qing-hua, Zhang Jing, Cai Jin-quan, Guo Jun-qi, Tang Min-ying, Shang Le-le, Tan Jian-ming
Organ Transplantation Institute, Fuzhou General Hospital, Fuzhou 350025, China.
Email:
Zhonghua Yi Xue Za Zhi. 2013 Dec 24;93(48):3841-6.
To establish a formula for estimating area under the concentration-versus-time curve (AUC) of mycophenolate sodium in Chinese renal allograft recipients with a limited sampling model.
A total of 35 renal allograft recipients were recruited from 2010 to 2013 to receive enteric-coated mycophenolate sodium (EC-MPS), calcineurin (CNI) and prednisone as immunosuppressive triple therapy. The serum concentration of mycophenolic acid (MPA) was assayed by enzyme multiplied immunoassay technique (EMIT) at pre-dose (C0), 0.5 (C0.5), 1.0 (C1), 1.5 (C1.5), 2.0 (C2), 3.0 (C3), 4.0 (C4), 6.0 (C6), 8.0 (C8) and 12.0 (C12) h post-dose respectively. Pharmacokinetic parameters of MPA (C0, C12, Cmax, Tmax, AUC0-12 h) were calculated by software WINNOLIN. Simplified formulae for estimation of MPA-AUC in tacrolimus (Tac) group or cyclosporin A (CsA) group were established by multiple stepwise regression analysis.
There were variable MPA AUC0-12 h levels between 14 and 67 mg×h/L (mean: 37 ± 14). The MPA trough level (C0) had no correlations with MPA AUC0-12 h (r(2) = 0.090) . The simplified MPA AUC formula for Tac group was AUC = 5.678+1.718×C4+2.853×C6+1.812×C8+3.413×C12 with four sampling points (C4, C6, C8, C12). Estimated AUC with the formula had correlations with AUC0-12 h (r(2) = 0.890). The mean absolute predict error (APE) was 3.45% (0.41%-24.71%) and the proportion of APE above 15% stood at 11.1% (2/18) . In CsA group, the simplified MPA AUC formula was AUC = 7.072+1.525×C3+1.558×C4+ 1.573×C6+2.285×C8. The correlation was r(2) = 0.952, mean APE was 6.50% (0.02%-12.91%) and proportion of APE above 15% stood at 0. The above formulae were observed to have agreement with AUC0-12 h by Bland-Altman analysis.
The simplified MPA AUC formulae with 4-point sampling provide an effective approach for estimating full MPA AUC0-12 h in Chinese renal recipients on EC-MPS plus tacrolimus or cyclosporin A.
采用有限采样模型建立估算中国肾移植受者霉酚酸钠浓度-时间曲线下面积（AUC）的公式。
选取2010年至2013年期间共35例肾移植受者，接受肠溶型霉酚酸钠（EC-MPS）、钙调神经磷酸酶抑制剂（CNI）和泼尼松作为三联免疫抑制治疗。分别于给药前（C0）、给药后0.5（C0.5）、1.0（C1）、1.5（C1.5）、2.0（C2）、3.0（C3）、4.0（C4）、6.0（C6）、8.0（C8）和12.0（C12）小时，采用酶放大免疫分析技术（EMIT）测定霉酚酸（MPA）的血清浓度。通过WINNOLIN软件计算MPA的药代动力学参数（C0、C12、Cmax、Tmax、AUC0-12 h）。通过多元逐步回归分析建立他克莫司（Tac）组或环孢素A（CsA）组估算MPA-AUC的简化公式。
MPA的AUC0-1 h水平在14至67 mg×h/L之间变化（均值：37±14）。MPA谷浓度（C0）与MPA的AUC0-12 h无相关性（r² = 0.090）。Tac组简化的MPA AUC公式为AUC = 5.678 + 1.718×C4 + 2.853×C6 + 1.812×C8 + 3.413×C12，有4个采样点（C4、C6、C8、C12）。用该公式估算的AUC与AUC0-12 h有相关性（r² = 0.890）。平均绝对预测误差（APE）为3.45%（0.41%-24.71%），APE高于15%的比例为11.1%（2/18）。在CsA组，简化的MPA AUC公式为AUC = 7.072 + 1.525×C3 + 1.558×C4 + 1.573×C6 + 2.285×C8。相关性为r² = 0.952，平均APE为6.50%（0.02%-12.91%），APE高于15%的比例为0。通过Bland-Altman分析观察到上述公式与AUC0-12 h具有一致性。
四点采样的简化MPA AUC公式为估算接受EC-MPS加他克莫司或环孢素A治疗的中国肾移植受者完整的MPA AUC0-12 h提供了一种有效的方法。
