Department of Pharmacology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Chin Med J (Engl). 2012 Dec;125(23):4226-32.
Mycophenolic acid (MPA) as an anti-proliferative immune-suppressive agent is used in the majority of immunosuppressive regimens in solid organ transplantation. This study aimed to investigate the pharmacokinetic (PK) characteristics of enteric-coated mycophenolate sodium (EC-MPS) and area under the curve (AUC) from 0 to 12 hours with limited sampling strategies (LSSs) in Chinese renal transplant recipients.
This study was conducted in 10 Chinese renal transplant patients receiving living donor and treated with EC-MPS, cyclosporine, and corticosteroids. MPA concentrations were measured by enzyme multiplied immunoassay technique (EMIT). Whole 12-hour PK profiles were obtained on Day 4 after operation. LSSs with jackknife technique, multiple stepwise regression analysis, and Bland-Altman analysis were developed to estimate MPA AUC.
The mean maximum plasma concentration, the mean time for it to reach peak (T(max)), and the mean MPA AUC were (11.38 ± 2.49) mg/L, (4.85 ± 3.32) hours, and (63.19 ± 13.54) mg×h×L(-1), respectively. Among the 10 profiles, MPA AUC of four patients was significantly higher than that of the other six patients, and the corresponding T(max) was significantly longer than that of the other six patients. No patient exhibited a second peak caused by enterohepatic recirculation. The best models were as follows: 27.46 + 0.94C(3) + 3.24C(8) + 2.81C(10) (r(2) = 0.972), which was used to predict AUC of fast metabolizer with a mean prediction error (MPE) of -0.21% and a mean absolute prediction error (MAE) of 2.59%; 36.65 + 3.08C(8) + 5.30C(10) - 4.04C(12) (r(2) = 0.992), which was used to predict AUC of slow metabolizer with a MPE of 0.58% and a MAE of 1.95%.
The PKs of EC-MPS had a high variability among Chinese renal transplant recipients. The preliminary PK data indicated the existence of slow and fast metabolizer. These findings may be associated with the enterohepatic recirculation.
霉酚酸（MPA）作为一种抗增殖免疫抑制剂，在实体器官移植中的大多数免疫抑制方案中都有使用。本研究旨在探讨中国肾移植受者中单剂量肠溶性吗替麦考酚钠（EC-MPS）的药代动力学（PK）特征和 0 至 12 小时的曲线下面积（AUC），采用有限采样策略（LSS）。
本研究纳入 10 例接受活体供者肾移植且接受 EC-MPS、环孢素和皮质类固醇治疗的中国肾移植患者。采用酶放大免疫测定技术（EMIT）测定 MPA 浓度。术后第 4 天获得 12 小时的全 PK 曲线。采用 Jackknife 技术、多元逐步回归分析和 Bland-Altman 分析建立 LSS 以估算 MPA AUC。
平均最大血浆浓度、达峰时间（T（max））和平均 MPA AUC 分别为（11.38±2.49）mg/L、（4.85±3.32）小时和（63.19±13.54）mg·h·L（-1）。在这 10 个 PK 曲线中，4 例患者的 MPA AUC 明显高于其他 6 例患者，相应的 T（max）明显长于其他 6 例患者。无患者出现肠肝再循环引起的双峰。最佳模型如下：27.46+0.94C（3）+3.24C（8）+2.81C（10）（r（2）=0.972），用于预测快代谢者的 AUC，平均预测误差（MPE）为-0.21%，平均绝对预测误差（MAE）为 2.59%；36.65+3.08C（8）+5.30C（10）-4.04C（12）（r（2）=0.992），用于预测慢代谢者的 AUC，MPE 为 0.58%，MAE 为 1.95%。
中国肾移植受者中单剂量肠溶性麦考酚钠的 PK 具有高度变异性。初步 PK 数据表明存在快代谢者和慢代谢者。这些发现可能与肠肝再循环有关。
