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Chemical Compound Review:

DHFU 5-fluoro-1,3-diazinane-2,4- dione

Synonyms: AGN-PC-00PZG0, AG-L-64219, SureCN2466350, AC1L3TSD, AC1Q6GJT, ...

Porter, D.J. et al., Maring, J.G. et al., Spector, T. et al., Sommadossi, J.P. et al., Aubert, C. et al.

Maring, Piersma, van Dalen, Groen, Uges, De Vries,

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Disease relevance of DHFU

We therefore tested the effects of (R)-5-fluoro-5,6-dihydrouracil (5-FUH2), the 5-FU catabolite extensively formed in the absence of 5-EU, on the antitumor activity and toxicity of 5-FU in 5-EU-treated rats bearing large s.c. tumors [1].
PURPOSE: The influence of liver metastases on the pharmacokinetics of 5-fluorouracil (5-FU) and its metabolite 5,6-dihydrofluorouracil (DHFU) was studied in patients with liver metastases from gastrointestinal cancer ( n=16) and compared with a control group of patients with nonmetastatic gastrointestinal cancer ( n=18) [2].

High impact information on DHFU

5-Fluorouracil and 5,6-dihydrofluorouracil, the two detected plasma metabolites, were quantitated by a gas chromatography-mass spectrometry methodology with a detection limit of 0.07 microM for both metabolites [3].
(R)-5-fluoro-5,6-dihydrouracil: kinetics of oxidation by dihydropyrimidine dehydrogenase and hydrolysis by dihydropyrimidine aminohydrolase [4].
Pharmacokinetics of 5-fluorouracil : impact of the measurement of the 5,6-dihydrofluorouracil [5].

Biological context of DHFU

The biologically active isomer of 5-fluoro-5,6-dihydrouracil [(R)-5-fluoro-5,6-dihydrouracil, R-FUH2] was synthesized to study the kinetics of its enzymatic oxidation and hydrolysis by homogeneous dihydropyrimidine dehydrogenase (DPDase) and dihydropyrimidine aminohydrolase (DPHase), respectively [4].

References

Attenuation of the antitumor activity of 5-fluorouracil by (R)-5-fluoro-5,6-dihydrouracil. Spector, T., Cao, S., Rustum, Y.M., Harrington, J.A., Porter, D.J. Cancer Res. (1995) [Pubmed]
Extensive hepatic replacement due to liver metastases has no effect on 5-fluorouracil pharmacokinetics. Maring, J.G., Piersma, H., van Dalen, A., Groen, H.J., Uges, D.R., De Vries, E.G. Cancer Chemother. Pharmacol. (2003) [Pubmed]
Kinetics and metabolism of a new fluoropyrimidine, 5'-deoxy-5-fluorouridine, in humans. Sommadossi, J.P., Aubert, C., Cano, J.P., Gouveia, J., Ribaud, P., Mathé, G. Cancer Res. (1983) [Pubmed]
(R)-5-fluoro-5,6-dihydrouracil: kinetics of oxidation by dihydropyrimidine dehydrogenase and hydrolysis by dihydropyrimidine aminohydrolase. Porter, D.J., Harrington, J.A., Almond, M.R., Lowen, G.T., Spector, T. Biochem. Pharmacol. (1994) [Pubmed]
Pharmacokinetics of 5-fluorouracil : impact of the measurement of the 5,6-dihydrofluorouracil. Aubert, C., Cano, J.P., Rigault, J.P., Seitz, J.F., Carcassonne, Y. Bulletin du cancer. (1981) [Pubmed]

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