Zhang Daping, Chow Diana S-L
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 1441 Moursund Street, Houston, TX, 77030, USA.
Eur J Drug Metab Pharmacokinet. 2017 Apr;42(2):183-189. doi: 10.1007/s13318-016-0378-6.
Mycophenolate mofetil (MMF), an ester prodrug of mycophenolic acid (MPA), is widely used as a maintenance immunosuppressive regimen in solid organ transplant patients. It is increasingly used for the prophylaxis and treatment of graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT) patients. MPA displays extensive binding to serum albumin and glucuronidation to the inactive MPA-7-O-glucuronide (MPAG). Here, we review and discuss the pertinent information regarding the clinical pharmacokinetics of MPA in HSCT patients. The pharmacokinetics of MPA are altered in HSCT patients with lower oral bioavailability, shorter half-life and higher clearance than those in healthy volunteers and renal transplant recipients. Moreover, clearance may be increased in young pediatric patients. The optimal MMF dosing and preferred targets are still under investigation in HSCT patients due to the substantial intra- and inter-individual pharmacokinetic variability of MPA and broad range of transplants (malignant vs. nonmalignant, related vs. unrelated donor, and human leukocyte antigen mismatch). The complex pharmacokinetics of MPA have partly hampered the efficient use of MMF, and pharmacokinetic studies in HSCT patients have been limited in size and mostly inconclusive. Future research should be multi-institutional and focus on developing clinical decisions with adequate statistical power to improve clinical care of HSCT recipients.
霉酚酸酯（MMF）是霉酚酸（MPA）的酯前体药物，在实体器官移植患者中广泛用作维持免疫抑制方案。它越来越多地用于造血干细胞移植（HSCT）患者移植物抗宿主病（GVHD）的预防和治疗。MPA与血清白蛋白广泛结合，并葡萄糖醛酸化形成无活性的MPA-7-O-葡萄糖醛酸苷（MPAG）。在此，我们回顾并讨论有关HSCT患者中MPA临床药代动力学的相关信息。与健康志愿者和肾移植受者相比，HSCT患者中MPA的药代动力学发生改变，口服生物利用度较低、半衰期较短且清除率较高。此外，年轻儿科患者的清除率可能会增加。由于MPA存在较大的个体内和个体间药代动力学变异性以及广泛的移植类型（恶性与非恶性、相关与无关供体以及人类白细胞抗原错配），HSCT患者中MMF的最佳给药剂量和首选靶点仍在研究中。MPA复杂的药代动力学在一定程度上阻碍了MMF的有效使用，并且HSCT患者的药代动力学研究规模有限且大多没有定论。未来的研究应多机构开展，并专注于制定具有足够统计学效力的临床决策，以改善HSCT受者的临床护理。
