Pirsch J D, Sollinger H W
Department of Medicine, University of Wisconsin Medical School, Madison, USA.
Ther Drug Monit. 1996 Aug;18(4):357-61. doi: 10.1097/00007691-199608000-00007.
Mycophenolate mofetil (MMF) is the first drug approved for the prevention of renal allograft rejection in the United States in the last 10 years. MMF is the morpholinoethyl ester of mycophenolic acid (MPA) and is a selective, reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme that is critical for the production of guanine monophosphate. MPA is a potent inhibitor of IMPDH, particularly the type II isoform. Compared with other cell types, lymphocytes appear to be more sensitive to inhibition of the type II isoform of IMPDH. This decreases the metabolism of guanine nucleotides, which are necessary for cell function. MMF is rapidly converted to MPA, which is the pharmacologically active drug. MPA is highly bound to serum albumin, and recent evidence suggests that the pharmacologic activity of MPA is a function of the unbound drug. Recent studies in human clinical transplantation have demonstrated the efficacy of this compound in renal transplantation. A major clinical study with > 1,499 patients demonstrated a 50% reduction in the incidence of acute rejection when compared with azathioprine or placebo control. The primary side effects in these studies were leukopenia, gastrointestinal problems, and cytomegalovirus disease. MMF represents a major advance in immunosuppression for renal transplant recipients. Ongoing studies are being performed in other types of solid organ transplantation.
霉酚酸酯（MMF）是过去10年中美国批准用于预防肾移植排斥反应的首个药物。MMF是霉酚酸（MPA）的吗啉代乙酯，是肌苷单磷酸脱氢酶（IMPDH）的选择性、可逆抑制剂，IMPDH是一种对鸟苷单磷酸生成至关重要的酶。MPA是IMPDH的强效抑制剂，尤其是II型同工酶。与其他细胞类型相比，淋巴细胞似乎对IMPDH II型同工酶的抑制更为敏感。这会降低细胞功能所必需的鸟嘌呤核苷酸的代谢。MMF迅速转化为MPA，MPA是具有药理活性的药物。MPA与血清白蛋白高度结合，最近的证据表明MPA的药理活性是游离药物的一种功能。近期在人类临床移植中的研究已证明该化合物在肾移植中的疗效。一项针对1499例以上患者的主要临床研究表明，与硫唑嘌呤或安慰剂对照相比，急性排斥反应的发生率降低了50%。这些研究中的主要副作用是白细胞减少、胃肠道问题和巨细胞病毒疾病。MMF代表了肾移植受者免疫抑制方面的一项重大进展。目前正在对其他类型的实体器官移植进行研究。
