Leeb B F, Smolen J S
2. Medizinischen Abteilung, Krankenhauses der Stadt Wien-Lainz.
Acta Med Austriaca. 1996;23(4):114-9.
Since the early eighties methotrexate (MTX) has become of increasing importance in long-term therapy of rheumatoid arthritis (RA) as a disease modifying drug (DMARD). Nowadays it is probably the most frequently prescribed DMARD for RA and can be regarded as the gold standard in long-term therapy. MTX can be administered orally or parenterally, the bioavailability shows high individual differences, but is about 70% after oral administration on average. Its protein-binding amounts to 50%, the main pathway of elimination is renal tubular secretion, to a smaller extent also biliary excretion. MTX polyglutamates are stored intracellularly. Its mode of action in RA is not completely elucidadet yet, besides inhibition of dihydrofolatereductase and consequently inhibition of thymidilate synthesis, some antiinflammatory effects, such as stimulation of Adenosine release from neutrophils, may contribute to the therapeutical effects. MTX' efficacy could be proven by several controlled trials, some of them lasting for more than five years. During long-term therapy with MTX a folate deficiency may occur, which can lead to some side effects. Most important but rarely occurring is pneumonitis, moreover hepatotoxicity and hematological features have to be intensively considered. The risk of the development of osteopenia or an increased incidence of malignancies during MTX therapy is currently investigated. In case of clinical and laboratory controls at regular intervals and patient education MTX therapy can be regarded as effective, well tolerable and considerably safe for patients with rheumatoid arthritis.
自20世纪80年代初以来,甲氨蝶呤(MTX)作为一种改善病情抗风湿药(DMARD),在类风湿关节炎(RA)的长期治疗中变得越来越重要。如今,它可能是RA最常处方的DMARD,可被视为长期治疗的金标准。MTX可以口服或胃肠外给药,其生物利用度存在很大的个体差异,但口服给药后平均约为70%。其蛋白结合率为50%,主要消除途径是肾小管分泌,在较小程度上也有胆汁排泄。MTX多聚谷氨酸在细胞内储存。它在RA中的作用方式尚未完全阐明,除了抑制二氢叶酸还原酶并因此抑制胸苷酸合成外,一些抗炎作用,如刺激中性粒细胞释放腺苷,可能有助于治疗效果。MTX的疗效已在多项对照试验中得到证实,其中一些试验持续了五年以上。在MTX长期治疗期间可能会出现叶酸缺乏,这可能导致一些副作用。最重要但很少发生的是肺炎,此外还必须密切考虑肝毒性和血液学特征。目前正在研究MTX治疗期间发生骨质减少或恶性肿瘤发病率增加的风险。如果定期进行临床和实验室检查并对患者进行教育,MTX治疗可被视为对类风湿关节炎患者有效、耐受性良好且相当安全。