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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)

19F nuclear magnetic resonance was used for a noninvasive and quantitative study of flucytosine (FC; 5-fluorocytosine) metabolism in two strains of Candida albicans and one strain of Candida tropicalis with various susceptibilities to FC. Three intracellular fluorinated metabolites were detected in the highly susceptible strain, F-nucleotides (Fnt), F-nucleosides, and 5-fluorouracil (5FU). Fnt were partially converted into 5FU when the spectra of the yeasts were recorded at 37 degrees C without perfusion, but the intensities of the signals were not modified at 4 or 37 degrees C if the cells were perfused. In the acid extract, the Fnt signal was resolved into three distinct peaks; none of them was attributable to 5-fluoro-2'-deoxyuridine-5'-monophosphate. The same signals were detected in the partially resistant strain, but only 5FU was observed in the highly resistant strain; the resistance of the latter strain therefore was primarily due to a defect in UMP pyrophosphorylase. At the end of the incubation period, only FC and released 5FU were present in the culture media. The concentration of the intracellular fluorinated metabolites was increased if the strain was susceptible to FC. The total amount of metabolized FC was very similar for the highly susceptible and the partially resistant strains, but the percentage of Fnt was much higher in the former (38%) than in the latter (8%); the mild resistance of the partially resistant strain therefore was attributed to the decreased activity of UMP pyrophosphorylase.