Schellens J H M, Beijnen J H
Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis, afd. Medische Oncologie, Plesmanlaan 121, 1066 CX Amsterdam.
Ned Tijdschr Geneeskd. 2007 Feb 10;151(6):337-41.
Intoxication due to insufficient renal clearance developed in 2 patients, a 54-year-old man and a 61-year-old woman, who were under treatment with methotrexate (MTX) for a primary cerebral lymphoma and a recurrence of large-cell B-cell-non-Hodgkin lymphoma, respectively. Both were treated with folinic acid rescue, thymidine, and alkalisation of the urine. MTX is a cytotoxic drug that is often used in oncology and rheumatology. Significant and even lethal toxicity can develop when the elimination ofMTX is delayed or when supportive care, such as folinic acid rescue, is inadequate. Delayed elimination can be caused by reduced renal function, by the 'third space' phenomenon such as in case of ascites, pleural fluid accumulation and oedema, and by drug-drug interactions leading to reduced renal function or a disturbance in the plasma protein binding ofMTX. Once toxicity has developed, the therapy must be directed at protection of the normal tissues, restoration of renal function and hence the renal elimination ofMTX, restoration of the alkalisation of the urine, and general supportive therapy.
两名患者出现了因肾脏清除不足导致的中毒情况，一名54岁男性和一名61岁女性，他们分别因原发性脑淋巴瘤和大细胞B细胞非霍奇金淋巴瘤复发而接受甲氨蝶呤（MTX）治疗。两人均接受了亚叶酸解救、胸腺嘧啶治疗以及尿液碱化处理。MTX是一种细胞毒性药物，常用于肿瘤学和风湿病学领域。当MTX的消除延迟或诸如亚叶酸解救等支持性治疗不足时，可能会出现显著甚至致命的毒性。消除延迟可能由肾功能减退、“第三间隙”现象（如腹水、胸腔积液积聚和水肿情况）以及导致肾功能减退或MTX血浆蛋白结合紊乱的药物相互作用引起。一旦发生毒性反应，治疗必须针对保护正常组织、恢复肾功能从而促进MTX经肾脏清除、恢复尿液碱化以及进行一般支持性治疗。
