Kinetics and metabolism of a new fluoropyrimidine, 5'-deoxy-5-fluorouridine, in humans.

Paper

Kinetics and metabolism of a new fluoropyrimidine, 5'-deoxy-5-fluorouridine, in humans.

Published Feb 1, 1983 · J. Sommadossi, C. Aubert, J. Cano

Cancer research

Q1 SJR score

29

Citations

0

Influential Citations

Semantic Scholar

Abstract

5'-Deoxy-5-fluorouridine (5'-dFUrd) is a new antineoplastic agent which possesses a higher therapeutic index in several experimental tumors compared to other fluoropyrimidines. During a Phase I trial, 5'-dFUrd, 1 to 15 g/sq m/week, was administered to patients as a 25- to 35-min i.v. infusion. Plasma kinetics and metabolism of 5'-dFUrd were investigated. The unmetabolized drug was measured by a high-performance liquid chromatography assay. 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. The disposition of 5'-dFUrd in humans at therapeutic doses followed a nonlinear kinetic process. Plasma concentrations of 5-fluorouracil generated in vivo represented approximately 6% of 5'-dFUrd concentrations and the 5-fluorouracil half-life ranged from 8.8 to 27.1 min. High plasma values of 5,6-dihydrofluorouracil (14.5 to 30 microM) were observed in patients, indicating the importance of this pathway in humans.

Non-RCT

Study Snapshot

5'-dFUrd, a new antineoplastic agent, shows promising kinetics and metabolism in humans, with high plasma levels of 5,6-dihydrofluorouracil.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Kinetics and metabolism of a new fluoropyrimidine, 5'-deoxy-5-fluorouridine, in humans.

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References

Quantitative analysis of 5-fluorouracil and 5,6-dihydrofluorouracil in plasma by gas chromatography mass spectrometry.

Gas chromatography mass spectrometry effectively quantifies 5-fluorouracil and 5,6-dihydro-5-fluorouracil in plasma, with biological applicability demonstrated in patients after intravenous administration of these drugs.

Selective activation of 5'-deoxy-5-fluorouridine by tumor cells as a basis for an improved therapeutic index.

5'-dFUrd has a higher therapeutic index due to its selective activation by sensitive tumor cells, rather than bone marrow cells, which can activate FUra, FUrd, and FdUrd.

Metabolism and biological activity of 5'-deoxy-5-fluorouridine, a novel fluoropyrimidine.

5'-dFUrd shows potential as an effective and less toxic antitumor agent due to its enzymatic conversion of FUra into biologically active nucleoside phosphorylase products.

Nonlinear pharmacokinetic models for 5‐fluorouracil in man: Intravenous and intraperitoneal routes

The two-compartment pharmacokinetic model for 5fluorouracil accurately predicts disappearance kinetics after intravenous bolus and steady-state levels during constant infusions, with a half-saturating concentration of 15M.

Comparative studies on the immunosuppressive effect among 5'-deoxy-5-fluorouridine, ftorafur, and 5-fluorouracil.

5'-DFUR has a less immunosuppressive effect than 5-fluorouracil and FT-207, with no significant reduction in spleen weight, thymus weight, or peripheral leucocyte number.

Tissue distribution of 5'-deoxy-5-fluorouridine and derived 5-fluorouracil in tumor-bearing mice and rats.

5'-deoxy-5-fluorouridine selectively transports 5-fluorouracil to cancer tissues, potentially enhancing its anticancer effect.

Tumor inhibitory effects of a new fluorouracil derivative: 5'-deoxy-5-fluorouridine.

5'-deoxy-5-fluorouridine (DFUR) shows strong antitumor activity against experimental tumors, with a more favorable antitumor activity-to-toxicity ratio than other fluorouracil derivatives.

Role of uridine phosphorylase for antitumor activity of 5'-deoxy-5-fluorouridine.

5'-Deoxy-5-fluorouridine (5'-DFUR) is a depot form of 5-fluorouracil that can be rapidly activated by uridine phosphorylase, contributing to its high chemotherapeutic index against various tumors.

Citations

The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold

Recent developments in nucleoside analogue antiviral drugs include complex modifications to the nucleoside scaffold, providing an informative historical perspective on successful and unsuccessful compounds.

Fluorine-Containing Diazines in Medicinal Chemistry and Agrochemistry

Fluorine-containing diazines offer new building blocks for the discovery of efficient fluorinated biologically active agents in medicinal and agrochemistry.

Uridine phosphorylase in breast cancer: a new prognostic factor?

Uridine phosphorylase (UPase) in breast cancer may be a new prognostic factor, as it contributes to the therapeutic efficacy of fluoropyrimidines and may influence the prognosis of breast cancer patients.

Clinical Development of new Fluoropyrimidines: A Major Improvement in Colorectal Cancer Treatment?

New fluoropyrimidines show potential in advanced colorectal cancer treatment, but their true advantage over fluorouracil requires further research and randomized trials.

Simultaneous determination of 5′-deoxy-5-fluorouridine, 5-fluorouracil and 5,6-dihydro-5-fluorouracil in serum by liquid chromatography with diode array UV detection

This study demonstrates a method for simultaneous determination of 5,6-dihydro-5-fluorouracil, 5-fluorouracil, and their anabolites in human serum using gradient elution-reversed phase liquid chromatography with diode array UV detection.