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Abstract

Direct detection of new flucytosine metabolites in human biofluids by 19F nuclear magnetic resonance.

J P Vialaneix, M C Malet-Martino, J S Hoffmann, J Pris and R Martino
Drug Metabolism and Disposition September 1987, 15 (5) 718-724;
J P Vialaneix
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M C Malet-Martino
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J S Hoffmann
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J Pris
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R Martino
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Abstract

19F nuclear magnetic resonance was used for the analysis of flucytosine (FC; 5-fluorocytosine) metabolites in biological fluids of a patient with cryptococcal meningitis who was intravenously injected with this drug at a daily dose of 7.5 g (2.5 g at 8-hr intervals). This method allows a direct, simultaneous, and quantitative determination of all the fluorinated metabolites of FC, in the range of sensitivity allowed by the spectrometer (sensitivity threshold, 0.01 mM). In urine, in addition to the already reported metabolites [unmetabolized FC and alpha-fluoro-beta-alanine (FBAL)], three new metabolites were identified: a glucuronide of FC (GLFC), 6-hydroxy-5-fluorocytosine (60HFC), and fluoride ion F-. The same metabolites (except F-) were found in plasma. In cerebrospinal fluid, only unchanged FC and GLFC were observed. The total urinary excretion during an 8-hr period between two injections of FC was 100.4% of the injected dose. Unchanged FC was the major excretory product accounting for 96.1% of the total. GLFC and 6OHFC made up, respectively, 2.7% and 1.2% of the excreted metabolites. The proportions of F- and FBAL were very low, respectively, 0.3% and 0.1% of the excreted metabolites. The global urinary excretion over a 24-hr period was 102% of the injected dose. The proportions of metabolites were very close to those obtained for the 8-hr period. In plasma, the proportions of metabolites were analogous to those determined in urine. In cerebrospinal fluid, GLFC represents 1% of the fluorinated metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

 

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Drug Metabolism and Disposition
Vol. 15, Issue 5
1 Sep 1987
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Abstract

Direct detection of new flucytosine metabolites in human biofluids by 19F nuclear magnetic resonance.

J P Vialaneix, M C Malet-Martino, J S Hoffmann, J Pris and R Martino
Drug Metabolism and Disposition September 1, 1987, 15 (5) 718-724;

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Abstract

Direct detection of new flucytosine metabolites in human biofluids by 19F nuclear magnetic resonance.

J P Vialaneix, M C Malet-Martino, J S Hoffmann, J Pris and R Martino
Drug Metabolism and Disposition September 1, 1987, 15 (5) 718-724;
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