甲氨蝶呤分解代谢在风湿性关节炎7-hydroxymethotrexate改变药物疗效和保留和减少叶酸。
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甲氨蝶呤分解代谢在风湿性关节炎7-hydroxymethotrexate改变药物疗效和保留和减少叶酸。
关节炎感冒。2009年8月,60 (8):2257 - 61。doi: 10.1002 / art.24685。
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19644884 (在PubMed]
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目的:评估甲氨蝶呤(MTX)的分解代谢7-hydroxy-MTX (7-OH-MTX)在类风湿性关节炎患者以及叶酸,叶酸的作用分解代谢。方法:尿排泄的MTX及其分解产物,7-OH-MTX,以2 MTX治疗后24小时尿标本收集。后从病人尿液样本收集的第六个和第七周剂量MTX。MTX和7-OH-MTX浓度的高效液相色谱测定质谱分析。肿胀和疼痛、压痛指数被用来衡量症状之前和在6和7周的治疗。患者接受叶酸或叶酸补充剂(1毫克/天)从6至7周。结果:叶酸抑制醛氧化酶(AO)所产生的酶7-OH-MTX,但叶酸没有。排泄7-OH-MTX(确定的比例的剂量MTX或毫克7-OH-MTX /通用肌酐)并不是正态分布(n = 39)。明显改善患者肿胀和疼痛、压痛指数平均7-OH-MTX排泄水平较低(P < 0.05)。病人叶酸补充剂降低了7-OH-MTX排泄(P = 0.03)。 Relatively high 7-OH-MTX excretion was correlated with relatively high MTX excretion and with relatively low MTX retention in vivo (P<0.05) (n=35). CONCLUSION: Our findings of a non-normal distribution of 7-OH-MTX excretion suggest that there are at least 2 phenotypes for this catabolism. Decreased 7-OH-MTX formation suggests folic acid inhibition of AO and a better clinical response, while increased 7-OH-MTX formation may interfere with MTX polyglutamylation and binding to enzymes and, therefore, may increase MTX excretion and decrease MTX retention and efficacy in vivo.