Schröder O, Stein J
Medizinische Klinik II, Johann-Wolfgang-Goethe-Universität, Frankfurt.
Z Gastroenterol. 1999 Jul;37(7):623-37.
This review is not only a comprehensive synopsis of the published data on methotrexate treatment for inflammatory bowel disease and primary biliary cirrhosis but gives also an overview about acting mechanisms, pharmacologic properties and limiting toxicities of low-dose methotrexate. Methotrexate and its polyglutamate analogues are structurally related to folic acid and inhibit many enzymes in the metabolic pathway of folic acid. Long-term low-dose methotrexate treatment (7.5-25 mg) inhibits production of thymidylate, purines, and methionine and leads to intracellulary accumulation of adenosin. These actions lead to inhibition of cellular proliferation, decreased formation of antibodies and reduced productions of inflammatory medicators. Several trials have demonstrated the efficacy of low-dose methotrexate therapy for certain indications as a promising new agent in the treatment of inflammatory bowel disease and primary biliary cirrhosis. However, several serious toxicities potentially limit its use.
本综述不仅全面概述了已发表的关于甲氨蝶呤治疗炎症性肠病和原发性胆汁性肝硬化的数据，还对低剂量甲氨蝶呤的作用机制、药理学特性和局限性毒性进行了概述。甲氨蝶呤及其聚谷氨酸类似物在结构上与叶酸相关，并抑制叶酸代谢途径中的许多酶。长期低剂量甲氨蝶呤治疗（7.5 - 25毫克）可抑制胸苷酸、嘌呤和蛋氨酸的生成，并导致细胞内腺苷积累。这些作用导致细胞增殖受到抑制、抗体形成减少以及炎症介质产生减少。多项试验已证明低剂量甲氨蝶呤治疗对某些适应症有效，是治疗炎症性肠病和原发性胆汁性肝硬化的一种有前景的新药。然而，几种严重的毒性可能会限制其使用。
