Cardiotoxicity of commercial 5-fluorouracil vials stems from the alkaline hydrolysis of this drug.
The cardiotoxicity of 5-fluorouracil (FU) was attributed to impurities present in the injected vials. One of these impurities was identified as fluoroacetaldehyde which is metabolised by isolated perfused rabbit hearts into fluoroacetate (FAC), a highly cardiotoxic compound. FAC was also detected in the urine of patients treated with FU. These impurities were found to be degradation products of FU that are formed in the basic medium employed to dissolve this compound. To avoid chemical degradation of this antineoplastic drug, the solution of FU that will be injected should be prepared immediately before use.
Lemaire
L
L
Laboratoire des IMRCP, Université Paul Sabatier, Toulouse, France.
Malet-Martino
M C
MC
de Forni
M
M
Martino
R
R
Lasserre
B
B
D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D000368:Aged; D000818:Animals; D004340:Drug Contamination; D005260:Female; D005463:Fluoroacetates / Q000633:toxicity*; D005472:Fluorouracil / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy*; D011817:Rabbits
D005463:Fluoroacetates; C075898:fluoroacetaldehyde; D000079:Acetaldehyde; D005472:Fluorouracil