Behrend M
Abteilung für Abdominal- und Transplantationschirurgie, Medical School Hannover, Germany.
Clin Nephrol. 1996 May;45(5):336-41.
This review gives a summary about the current knowledge on the novel immunosuppressive drug mycophenolate mofetil (RS61443) in renal transplantation. The results of the preclinical pilot trials and of the so far published pivotal study for the prevention of rejection are described. Mycophenolate mofetil (MMF), the 2-4-morpholino ethyl ester of mycophenolic acid, is an inhibitor of the Inosine Monophosphate Dehydrogenase, an enzyme in the de novo synthesis of purines. MMF showed no clinical significant interactions with a variety of medications used in renal transplantation. Following oral administration it is rapidly absorbed. Pilot studied suggested a significant reduction in the incidence of rejection at doses of 2 g/day. 491 patients were enrolled in a randomized, double blind, multicentre, placebo-controlled study of the addition of mycophenolate mofetil to cyclosporine and oral corticosteroids for the prevention of acute renal allograft rejection. After six month the rates for biopsy proven rejection were the following: placebo 46.4%, MMF 2 g 17.0% and MMF 3 g 13.8%. The adverse event profile resembles that of triple therapy with azathioprine. Most adverse events concerned the gastrointestinal tract, the hemic system and opportunistic infections. MMF offers an improved immunosuppressive therapy following renal transplantation.
本综述总结了新型免疫抑制药物霉酚酸酯（RS61443）在肾移植方面的现有知识。文中描述了预防排斥反应的临床前试验结果以及迄今为止已发表的关键研究结果。霉酚酸酯（MMF）是霉酚酸的2-4-吗啉代乙酯，是肌苷单磷酸脱氢酶的抑制剂，该酶参与嘌呤的从头合成。MMF与肾移植中使用的多种药物无临床显著相互作用。口服后它能迅速被吸收。初步研究表明，每日剂量为2克时，排斥反应发生率显著降低。491名患者参与了一项随机、双盲、多中心、安慰剂对照研究，该研究将霉酚酸酯添加到环孢素和口服皮质类固醇中以预防急性肾移植排斥反应。六个月后，经活检证实的排斥反应发生率如下：安慰剂组为46.4%，MMF 2克组为17.0%，MMF 3克组为13.8%。不良事件情况与硫唑嘌呤三联疗法相似。大多数不良事件涉及胃肠道、血液系统和机会性感染。MMF为肾移植后的免疫抑制治疗提供了更好的选择。
