ISSN:
1432-0843
Keywords:
Key words Fluorouracil
;
Stability
;
Cardiotoxic compounds
;
Ambulatory pump
;
Lyophilizate
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Purpose: The stability of 5-fluorouracil (FU) Roche solutions in a portable infusion pump under prolonged “in-use” conditions (32 °C, in the dark) was studied, especially with respect to the formation of the cardiotoxic compounds fluoroacetaldehyde (Facet) and fluoromalonic acid semialdehyde (FMASAld). Methods: The solutions, prepared according to three protocols frequently used at the Anticancer Centre in Toulouse, were analysed by 19F NMR immediately after preparation (T0) and after 2, 3 or 10 days (TF) in the pump. Results: The commercial solution already contained 64 fluorinated “impurities”, among them fluoride ion (F−), FMASAld and Facet. The concentration of FU did not change significantly between T0 and TF, whatever the protocol. The levels of F− had not increased significantly after 2 or 3 days, but had increased by about 50% after 10 days. The increases in FMASAld levels were low (12–28%) albeit significant in the three protocols. The levels of Facet had increased by a factor of about 2 after 2 or 3 days, and by a factor of 〉3 after 10 days. The levels of the other fluorinated compounds were constant during the first 2 or 3 days, but had increased by about 30% after 10 days. FU Dakota lyophilizates, analysed immediately after reconstitution, contained neither FMASAld nor Facet. After 2 days at 25 °C, low levels of FMASAld were present but Facet could still not be detected. Conclusion: This study showed that special attention must be paid to the risk of increasing concentrations of highly toxic FMASAld and Facet when FU is administered via a pump for long periods of time. It would be preferable not to exceed 3 days of treatment when patients receive FU from a portable infusion pump. This underlines the interest in using a lyophilized formulation of FU in clinical practice.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002800000182
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