Kruck T P, Fisher E A, McLachlan D R
Department of Physiology, University of Toronto, Ontario, Canada.
Clin Pharmacol Ther. 1990 Oct;48(4):439-46. doi: 10.1038/clpt.1990.173.
Deferoxamine treatment may produce serious side effects that can be eliminated by modification of treatment and by control of deferoxamine metabolism. A patient suffering from dementia of the Alzheimer type with normal liver and kidney function who was treated with deferoxamine initially tolerated a dose of 7 mg/kg deferoxamine mesylate injected intramuscularly twice a day for a total of 5 days a week. After several months nausea and weight loss gradually developed in the patient that could be controlled initially by dose reduction, leading to levels inappropriate for aluminum chelation. HPLC analysis of blood and urine revealed several metabolites including, as a major component, a plasma monoamine oxidase (MAO) catalyzed end product MFO1. Coadministration of isoniazid, a plasma MAO inhibitor, with deferoxamine resulted in reduction of MFO1 from 81% to 8% accompanied by increases in the amounts of metabolite 2 (MFO2) from 2% to 24% and unmetabolized deferoxamine from 17% to 68% after 6 months of treatment. The side effects subsided, the patient regained weight, and treatment could be continued.
去铁胺治疗可能会产生严重的副作用，通过调整治疗方法和控制去铁胺代谢可以消除这些副作用。一名患有阿尔茨海默型痴呆且肝肾功能正常的患者，最初接受去铁胺治疗时，耐受每天两次肌肉注射7毫克/千克甲磺酸去铁胺的剂量，每周共注射5天。几个月后，患者逐渐出现恶心和体重减轻的症状，最初可通过减少剂量来控制，但导致铝螯合所需的水平不合适。血液和尿液的高效液相色谱分析显示有几种代谢产物，其中主要成分是血浆单胺氧化酶（MAO）催化的终产物MFO1。在治疗6个月后，同时给予血浆MAO抑制剂异烟肼与去铁胺，结果MFO1从81%降至8%，同时代谢产物2（MFO2）的量从2%增加到24%，未代谢的去铁胺从17%增加到68%。副作用消退，患者体重恢复，治疗得以继续。
