Wang Zuoyi, He J J, Liu X Y, Lin Bingyi, Zhang Lin, Geng Lei, Zheng Shusen
a Division of Hepatobiliary and Pancreatic Surgery , Department of Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
Immunopharmacol Immunotoxicol. 2015;37(6):508-12. doi: 10.3109/08923973.2015.1096286. Epub 2015 Nov 2.
The management of liver receivers requires intense immunosuppression to prevent graft rejection. Mycophenolate mofetil (MMF) is a common immunosuppressant but frequently suffer dose reduction for gastrointestinal adverse reactions (GI). Hence, the enteric-coated mycophenolate sodium (EC-MPS) is introduced as a substitute for MMF to reduce GI. The study was designed to investigate the efficacy, safety and exposure equation of EC-MPS in liver transplant patients in China.
Ninety-two liver receivers who administered EC-MPS or MMF as a primary immunosuppressant were enrolled in this single-center study and divided into MMF group and EC-MPC group, respectively. Efficacy and safety of EC-MPS were compared with MMF. The MPA exposure was measured at time 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 h after mean 4.5 days of EC-MPS treatment. An equation of limited time points for estimating serum MPA exposure of EC-MPS was established using multiple stepwise regression model.
Data show an interpatient variation in MPA AUC, Cmax and Tmax. After a first dose of EC-MPS, the mean value of serum AUC0-12 h was 20.68 mg/L (SD 8.94, range 8.1-46.3). Cmax was 9.7 mg/L (SD 6.48, range 2.7-16.3); Tmax was 1.90 h (SD 0.97, range 0.5-4). The best equation for estimating the AUC was 6.0 1 4 + 0.946C2 + 0.606C3 + 1.154C4 + 2.479C6 + 5.07C12. Comparing with MMF, EC-MPS not only effectively maintained immunosuppression, but also had similar incidences of infection, renal dysfunction and hematological disorders. However, EC-MPS markedly improved GI, the incidence of GI was half of the MMF group.
This analysis presented that EC-MPS is an effective and safe immunosuppressant as similar as MMF. The conversion of MMF to EC-MPS could be administered.
肝移植受者的管理需要强化免疫抑制以预防移植物排斥反应。霉酚酸酯（MMF）是一种常用的免疫抑制剂，但常因胃肠道不良反应（GI）而减少剂量。因此，肠溶型霉酚酸钠（EC-MPS）被引入作为MMF的替代品以减少胃肠道不良反应。本研究旨在探讨EC-MPS在中国肝移植患者中的疗效、安全性及暴露量方程。
本单中心研究纳入了92例将EC-MPS或MMF作为主要免疫抑制剂的肝移植受者，分别分为MMF组和EC-MPC组。比较EC-MPS与MMF的疗效和安全性。在EC-MPS治疗平均4.5天后的0、0.5、1、1.5、2、3、4、6、8、12小时测量霉酚酸（MPA）暴露量。使用多元逐步回归模型建立了用于估计EC-MPS血清MPA暴露量的有限时间点方程。
数据显示患者间MPA的曲线下面积（AUC）、峰浓度（Cmax）和达峰时间（Tmax）存在差异。首次服用EC-MPS后，血清AUC0-12h的平均值为20.68mg/L（标准差8.94，范围8.1-46.3）。Cmax为9.7mg/L（标准差6.48，范围2.7-16.3）；Tmax为1.90小时（标准差0.97，范围0.5-4）。估计AUC的最佳方程为6.014 + 0.946C2 + 0.606C3 + 1.154C4 + 2.479C6 + 5.07C12。与MMF相比，EC-MPS不仅有效维持了免疫抑制，而且感染、肾功能不全和血液系统疾病的发生率相似。然而，EC-MPS显著改善了胃肠道不良反应，其发生率是MMF组的一半。
本分析表明EC-MPS是一种与MMF相似的有效且安全的免疫抑制剂。可以将MMF转换为EC-MPS进行给药。
