A predictor for side effects in patients with Alzheimer's disease treated with deferoxamine mesylate.
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.
Kruck
T P
TP
Department of Physiology and Medicine, University of Toronto, Ontario, Canada.
Fisher
E A
EA
McLachlan
D R
DR
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000855:Anorexia / Q000139:chemically induced; D002851:Chromatography, High Pressure Liquid; D003676:Deferoxamine / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008995:Monoamine Oxidase / Q000652:urine; D011897:Random Allocation
D008995:Monoamine Oxidase; D003676:Deferoxamine