Sollinger H W
Department of Surgery, University of Wisconsin, Madison, USA.
Kidney Int Suppl. 1995 Dec;52:S14-7.
Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid (MPA), is a new selective immunosuppressant used for the prevention and treatment of acute renal rejection after transplantation. In vivo MMF is deesterified to MPA, which is a potent and specific inhibitor of de novo purine synthesis and suppressor of both T and B lymphocyte proliferation. In animal studies, MMF has been shown to be effective in prolonging the survival of allografts and xenografts in rodents, dogs, and monkeys. Experimental evidence in animal models suggests that MMF also may be effective in the treatment of chronic vascular rejection. A phase I clinical trial showed MMF was well tolerated in renal transplant patients at doses up to 3,500 mg/day for up to two years. There was no correlation between the incidence of adverse effects and dose of MMF, and no overt nephrotoxicity, hepatotoxicity, or myelotoxicity was observed. In a multicenter study in patients with biopsy-proven renal allograft rejection, successful rescue (stabilization or improvement of renal function) was achieved with MMF in combination with maintenance doses of cyclosporine and prednisone in 69% of patients. This result suggested that MMF may be effective in the treatment of renal allograft rejection after transplantation. In a large multicenter trial, MMF in combination with cyclosporine and prednisone was superior to a standard immunosuppressive regimen including azathioprine. Taken together, the data indicate that MMF will be a valuable addition to the list of immunosuppressants available for the prevention and treatment of renal rejection after transplantation.
霉酚酸酯（MMF），即霉酚酸（MPA）的吗啉代乙酯，是一种新型选择性免疫抑制剂，用于预防和治疗移植后急性肾排斥反应。在体内，MMF脱酯形成MPA，MPA是一种强效且特异性的从头嘌呤合成抑制剂，可抑制T和B淋巴细胞增殖。在动物研究中，MMF已被证明可有效延长啮齿动物、狗和猴子同种异体移植物和异种移植物的存活时间。动物模型中的实验证据表明，MMF在治疗慢性血管排斥反应方面也可能有效。一项I期临床试验表明，肾移植患者对高达3500mg/天的MMF剂量耐受性良好，持续用药长达两年。不良反应发生率与MMF剂量之间无相关性，未观察到明显的肾毒性、肝毒性或骨髓毒性。在一项针对经活检证实的肾移植排斥反应患者的多中心研究中，69%的患者使用MMF联合维持剂量的环孢素和泼尼松成功挽救（肾功能稳定或改善）。该结果表明，MMF可能对治疗移植后肾移植排斥反应有效。在一项大型多中心试验中，MMF联合环孢素和泼尼松优于包括硫唑嘌呤在内的标准免疫抑制方案。综上所述，这些数据表明，MMF将成为可用于预防和治疗移植后肾排斥反应的免疫抑制剂列表中的一个有价值的补充药物。
