Authors: Robert Martino; Myriam Malet-Martino; Veronique Gilard

Source: Current Drug Metabolism, Volume 1, Number 3, November 2000 , pp. 271-303(33)

Publisher: Bentham Science Publishers

Abstract:

Fluorine-19 nuclear magnetic resonance (19F NMR) spectroscopy provides a highly specific tool for identifying fluorine-containing drugs and their metabolites in biological media. This article focuses on the application of 19F NMR to the metabolic studies of fluoropyrimidine drugs in clinical use. The value and difficulties encountered in investigations on drug metabolism are first discussed. The metabolism and disposition studies of the anticancer drug 5-fluorouracil, the mainstay of antimetabolite treatment for solid tumors, and its prodrugs, doxifluridine and capecitabine, are then extensively reviewed. The studies dealing with the antimycotic agent, 5-fluorocytosine, as well as the novel anticancer drug, gemcitabine, are also considered. From in vitro (biofluids or tissue extracts) 19F NMR analysis, seven new metabolites of 5- fluorouracil, doxifluridine, capecitabine and 5-fluorocytosine were identified. Except two, they were only detected using this technique. This emphasizes the high analytical potential of in vitro 19F NMR. In vivo 19F NMR is non-invasive and thus allows the quantitative monitoring of the metabolism of 5-fluorouracil in the target tissue, e.g. the tumor, as well as its biodistribution. Another promising application is its ability to estimate the level of yeast cytosine deaminase gene expression in human tumors from the quantitative monitoring of 5-fluorouracil formation from the non-cytotoxic drug 5-fluorocytosine. Notwithstanding these successes, the limited sensitivity and spectral resolution of 19F NMR precludes its extensive applicability to all the fluorinated drugs.

Keywords: Fluorine; 5-fluorocytosine; doxifluridine; capecitabine; 19F NMR

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389200003339036

Affiliations: 1: Biomedical NMR Group, IMRCP Laboratory, Universite Paul Sabatier, 118, route de Narbonne, 31062 Toulouse, France.

Publication date: 2000-11-01

More about this publication?

• Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:
  
  In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.

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