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The tris formulation of Fluorouracil is more cardiotoxic than the sodium-salt formulations
L Lemaire1, M Maletmartino, R Martino
1UNIV TOULOUSE 3,IMRCP LAB,RMN BIOMED GRP,F-31062 TOULOUSE,FRANCE. INST GUSTAVE ROUSSY,F-77176 SAVIGNY,FRANCE. INST PHYSIOL,EQUIPE PHARMACOL REGULAT,F-31400 TOULOUSE,FRANCE.
Abstract:
The cardiotoxicity of 5-fluorouracil (FU) was attributed to degradation compounds present in the injected vials, fluoroacetaldehyde (Facet) and fluoromalonaldehydic acid (FMald). FU-NaOH vials were much less cardiotoxic than FU-Tris vials on the isolated perfused rabbit heart model since Facet and FMald are stored in stable depot forms in FU-Tris vials whereas, in FU-NaOH vials, they are extensively transformed. Cardiotoxic fluoroacetate (FAG), coming from Facet metabolization, was found in urine of patients, with a ratio FAC /FU catabolites 10-30 fold lower in patients treated with FU-NaOH than in those treated with FU-Tris.
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