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霉酚酸酯——一种新型免疫抑制剂

[Mycophenolate mofetil--a new immunosuppressive agent].

作者信息

Bergan S, Albrechtsen D, Fauchald P

机构信息

Institutt for klinisk biokjemi, Rikshospitalet, Oslo.

出版信息

Tidsskr Nor Laegeforen. 1996 Aug 30;116(20):2439-41.

PMID:8928103
Abstract

Mycophenolate mofetil is a prodrug that is rapidly converted to the active immunosuppressant mycophenolic acid. This substance inhibits the enzyme inosine monophosphate dehydrogenase, leading to a depletion of (deoxy-)guanosine nucleotides and thereby a reduction of de novo purine synthesis. Lymphocytes are relatively dependent on this pathway, particularly for RNA and DNA synthesis, and are thereby more susceptible to the antiproliferative effects of mycophenolate. In three randomised, double-blind, multicentre trials, lower rejection rates have been demonstrated in renal allograft recipients during the first months after transplantation. Side effects were more frequent in the mycophenolate mofetil groups. The most important adverse reactions to mycophenolate mofetil are leucopenia, gastrointestinal effects and the increased risk of infections and malignancies associated with immunosuppression in general. At 12 months, graft survival was similar in all groups. The future role of mycophenolate mofetil in immunosuppressive therapy during transplantation has not yet been established. As a start it may be found to have specific use in subgroups of allograft recipients at high risk of rejection.

摘要

霉酚酸酯是一种前体药物,可迅速转化为活性免疫抑制剂霉酚酸。该物质抑制肌苷单磷酸脱氢酶,导致(脱氧)鸟苷核苷酸耗竭,从而减少嘌呤从头合成。淋巴细胞相对依赖于该途径,尤其是对于RNA和DNA合成,因此更容易受到霉酚酸酯抗增殖作用的影响。在三项随机、双盲、多中心试验中,肾移植受者在移植后的头几个月内排斥反应发生率较低。霉酚酸酯组的副作用更为常见。霉酚酸酯最重要的不良反应是白细胞减少、胃肠道反应以及与免疫抑制相关的感染和恶性肿瘤风险增加。在12个月时,所有组的移植物存活率相似。霉酚酸酯在移植免疫抑制治疗中的未来作用尚未确定。一开始,它可能被发现对排斥反应高风险的移植受者亚组有特定用途。

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