THE TRIS FORMULATION OF FLUOROURACIL IS MORE CARDIOTOXIC THAN THE SODIUM-SALT FORMULATIONS
Résumé
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.