Kruck T P, Fisher E A, McLachlan D R
Department of Physiology and Medicine, University of Toronto, Ontario, Canada.
Clin Pharmacol Ther. 1993 Jan;53(1):30-7. doi: 10.1038/clpt.1993.6.
In a previously reported clinical trial, patients with Alzheimer's disease were treated with deferoxamine mesylate, which resulted in a 50% reduction in the average rate of deterioration over 2 years. There were five deaths in the untreated group during the trial and no deaths in the treated group, although five of 25 treated patients reported anorexia. Deferoxamine metabolite analysis of urine for 24 hours after deferoxamine injection from sensitive and nonsensitive patients showed marked differences. Occurrence of side effects correlated with increased formation of a monoamine oxidase catalyzed (major) metabolite, MFO1. The metabolite ratio, MFO1/total metabolites, plus parent drug (TOT) showed a bimodal distribution with a mean +/- SD value of 0.68 +/- 0.06 for the nonsensitive and 0.79 +/- 0.04 for sensitive patients. The MFO1/TOT ratio discriminates between sensitive and nonsensitive patients, and we suggest that the half difference mark between the two mean values (0.735) can be used as a predictor of side effects. Patients with a MFO1/TOT ratio of greater than 0.70 would be considered at risk and observed for onset of side effects. Patients with a MFO1/TOT ratio greater than 0.80 would be considered for immediate adjunct treatment with isoniazid or other monoamine oxidase inhibitors.
在之前报道的一项临床试验中，阿尔茨海默病患者接受了甲磺酸去铁胺治疗，结果两年内平均恶化率降低了50%。试验期间，未治疗组有5例死亡，治疗组无死亡，尽管25例接受治疗的患者中有5例报告有厌食症状。对敏感和不敏感患者注射去铁胺后24小时尿液中的去铁胺代谢物分析显示出显著差异。副作用的发生与单胺氧化酶催化的（主要）代谢物MFO1生成增加相关。代谢物比率，即MFO1/总代谢物加母体药物（TOT），呈现双峰分布，不敏感患者的平均±标准差为0.68±0.06，敏感患者为0.79±0.04。MFO1/TOT比率可区分敏感和不敏感患者，我们建议两个平均值之间的半差值标记（0.735）可作为副作用的预测指标。MFO1/TOT比率大于0.70的患者将被视为有风险，并观察副作用的发生。MFO1/TOT比率大于0.80的患者将考虑立即用异烟肼或其他单胺氧化酶抑制剂进行辅助治疗。
