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  • Title: Evidence for the importance of 5'-deoxy-5-fluorouridine catabolism in humans from 19F nuclear magnetic resonance spectrometry.
    Author: Malet-Martino MC, Armand JP, Lopez A, Bernadou J, Béteille JP, Bon M, Martino R.
    Journal: Cancer Res; 1986 Apr; 46(4 Pt 2):2105-12. PubMed ID: 2936452.
    Abstract:
    The use of a new methodology, 19F nuclear magnetic resonance, has allowed detection of all the fluorinated metabolites in the biofluids of patients treated with 5'-deoxy-5-fluorouridine (5'-dFUrd) injected i.v. at a dose of 10 g/m2 over 6 h. This technique, which requires no labeled drug, allows a direct study of the biological sample with no need for extraction or derivatization and a simultaneous identification and quantitation of all the different fluorinated metabolites. As well as the already known metabolites, unmetabolized 5'-dFUrd, 5-fluorouracil, and 5,6-dihydro-5-fluorouracil, the presence of alpha-fluoro-beta-ureidopropionic acid, alpha-fluoro-beta-alanine (FBAL), N-carboxy-alpha-fluoro-beta-alanine, and the fluoride anion F- is reported. The catabolic pathway proposed for 5'-dFUrd is analogous to that of 5-fluorouracil, completed with FBAL----F- step, and the plasmatic equilibrium of FBAL with N-carboxy-alpha-fluoro-beta-alanine, its N-carboxy derivative. The quantitative analysis of the different metabolites found in plasma and urine emphasizes the significance of the catabolic pathway. High concentrations of alpha-fluoro-beta ureidopropionic acid and FBAL are recovered in plasma from 3 h after the beginning of the perfusion to 1 h after its end. The global urinary excretion results show that there is a high excretion of 5'-dFUrd and metabolites. Unchanged 5'-dFUrd and FBAL are by far the major excretory products and are at nearly equal rates. The protocol followed in this study produces relatively low but persistent plasmatic concentrations of 5-fluorouracil throughout the perfusion.
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