Suppression of deferoxamine mesylate treatment-induced side effects by coadministration of isoniazid in a patient with Alzheimer's disease subject to aluminum removal by ionspecific chelation

• Published in: Clinical pharmacology and therapeutics Vol. 48; no. 4; p. 439
• Main Authors: Kruck, T P, Fisher, E A, McLachlan, D R
• Format: Journal Article
• Language: English
• Published: United States 01-10-1990
• Subjects: Aluminum; Alzheimer Disease - drug therapy; Chelation Therapy; Chromatography, High Pressure Liquid; Deferoxamine - administration & dosage; Deferoxamine - adverse effects; Deferoxamine - therapeutic use; Drug Therapy, Combination; Humans; Injections, Intramuscular; Isoniazid - administration & dosage; Isoniazid - blood; Isoniazid - therapeutic use; Isoniazid - urine; Monoamine Oxidase - blood; Pyridoxine - administration & dosage; Pyridoxine - blood; Pyridoxine - therapeutic use; Pyridoxine - urine
• ISSN: 0009-9236
• 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.