Department of Pharmacy, Kagawa University Hospital, Kagawa, Japan.
Biol Pharm Bull. 2013;36(6):1036-9. doi: 10.1248/bpb.b12-01095. Epub 2013 Apr 5.
Mycophenolate mofetil (MMF) is used for oral administration to prevent rejection in renal transplant recipients, and is rapidly converted into mycophenolic acid (MPA), the active metabolite, by hydrolysis in vivo. The area under the concentration-time curve (AUC(0-12 h)) of MPA is considered to be an effective pharmacokinetics parameter for predicting acute rejection. However, frequent blood sampling is required to calculate AUC(0-12 h), which imposes a burden on patients and providers. Therefore, we examined a limited sampling strategy (LSS) for estimation of MPA-AUC(0-12 h) using only a trough level (C0) and two points including C0 in Japanese living-related renal transplant recipients with concomitant extended-release tacrolimus (ER-TAC). The present study suggests that better estimation of MPA-AUC(0-12 h) can be obtained by using two points including C0 as compared with only C0 regardless of transplant progress. Furthermore, blood collection points showing the highest estimation of MPA-AUC(0-12 h) by adding to C0 were C4 at pre-transplantation (Tx) and 1 month post-Tx, and C6 at 3 months post-Tx. We conjecture that changes in renal function and serum albumin (Alb) accompanying transplant progress are aggravating factors in terms of estimation, because there was also a significant difference in the reciprocal of serum creatinine (1/Scr) and Alb between pre-Tx and post-Tx in this study. In conclusion, the present study provides useful information for effective and efficient monitoring of MPA levels in Japanese living-related renal transplant recipients.
霉酚酸酯(MMF)用于口服以预防肾移植受者的排斥反应,并且在体内通过水解迅速转化为活性代谢物霉酚酸(MPA)。MPA 的浓度-时间曲线下面积(AUC(0-12 h))被认为是预测急性排斥反应的有效药代动力学参数。然而,计算 AUC(0-12 h) 需要频繁采血,这给患者和提供者带来了负担。因此,我们在伴有他克莫司延长释放制剂(ER-TAC)的日本活体亲属肾移植受者中,检查了一种仅使用谷浓度(C0)和包括 C0 的两点的有限采样策略(LSS)来估算 MPA-AUC(0-12 h)。本研究表明,与仅使用 C0 相比,无论移植进展如何,使用包括 C0 的两点可以更好地估算 MPA-AUC(0-12 h)。此外,通过在 C0 基础上增加采血点,显示出对 MPA-AUC(0-12 h)最高估算值的采血点为移植前(Tx)的 C4 和 Tx 后 1 个月的 C6,以及 Tx 后 3 个月的 C6。我们推测,随着移植进展,肾功能和血清白蛋白(Alb)的变化是估算的加重因素,因为在本研究中,Tx 前后血清肌酐(1/Scr)和 Alb 的倒数也存在显著差异。总之,本研究为日本活体亲属肾移植受者中 MPA 水平的有效和高效监测提供了有用信息。