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The antineoplastic ifosfamide produces dose-dependent signs of neurotoxicity.After ifosfamide overdose in a patient,we found excessive urinary excretion of glutaric acid and sarcosine,which is compatible with glutaric aciduria type II,a defect in mitochondrial fatty acid oxidation that results from defective electron transfer to flavoproteins.We therefore used the electron-accepting drug methylene-blue as an antidote for ifosfamide encepahlopathy.In one patient,ifosfamide neurotoxicity was rapidly reversed by methylene-blue 50 mg intravenously.In another patient with previous episodes of ifosfamide encephalopathy,methylene-blue was administered orally prophylactically.No symptoms of neurotoxicity were noted. |
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