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Flucytosine conversion to fluorouracil in humans: Does a correlation with gut flora status exist? A report of two cases using fluorine-19 magnetic resonance spectroscopy

Konversion von Flucytosin zu Fluorouracil beim Menschen: Bezug zur Zusammensetzung der Darmflora? Bericht über Untersuchungen an zwei Fällen mittels Fluor-19 Magnet-Resonanz-Spektroskopie

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Summary

A relationship between the gut flora level, particularly gram-negative enterobacilli, and thein vivo flucytosine conversion to fluorouracil has been observed in humans from the fluorine-19 magentic resonance spectroscopy analysis of urine from two patients treated with the flucytosine- (6 to 9 g/day) amphotericin B (1 mg/kg/day) combination. Indeed the percentage of fluorouracil metabolites was extremely low (<0.6% of total fluorinated compounds excreted) when the number of enterobacillary colonies was low (<103) and higher (3.5 to 8.8%) when enterobacillary colonies were under reconstitution or in the normal range (105 to 108). The intestinal microflora assessment may therefore be of high interest to predict the risk of an additive flucytosine-induced myelotoxicity suspected to be due to fluorouracil during flucytosine chronic therapy.

Zusammenfassung

Bei zwei Patienten fand sich eine Beziehung zwischen der Zusammensetzung der Darmflora, vor allem dem Anteil gramnegativer Stäbchenbakterien und derIn-vivo-Konversion von Flucytosin zu Fluorouracil, die während Behandlung mit der Kombination Flucytosin (6 bis 9 g pro Tag) plus Amphotericin B (1 mg/kg/Tag) durch Fluor-19 Magnet-Resonanz-Spektroskopie im Urin nachgewiesen wurde. Der Anteil des Fluorouracil-Metabolite war mit weniger als 0,6% der gesamten im Urin ausgeschiedenen fluorierten Verbindungen extrem niedrig solange die Koloniebildnerzahlen der Enterobazillen unter 103 lagen. Der prozentuale Anteil von Fluorouracil stieg auf 3,5 bis 8,8% an während sich die Enterobazillen erholten oder normalisierten und Koloniebildnerzahlen von 105 bis 108 erreichten. Die Kontrolle der Darmflora unter langfristiger Anwendung von Flucytosin ergibt möglicherweise hochinteressante Anhaltspunkte für eine Vorhersage des myelotoxischen Risikos durch den Metaboliten Fluorouracil.

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Authors and Affiliations

  1. Biomedical NMR Group, IMRCP Laboratory, Université Paul Sabatier, 118, route de Narbonne, F-31062, Toublouse Cédex

    Marie-Catherine Malet-Martino Ph.D. & R. Martino Ph.D.

  2. Centre Claudius Regaud, 20-24 rue du Pont Saint Pierre, F-31000, Toulouse

    M. de Forni M.D.

  3. Institut Gustave Roussy, rue Camille Desmoulins, F-94805, Villejuif Cédex, France

    A. Andremont M.D., O. Hartmann M.D. & J. P. Armand M.D.

Authors
  1. Marie-Catherine Malet-Martino Ph.D.
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  2. R. Martino Ph.D.
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  3. M. de Forni M.D.
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  4. A. Andremont M.D.
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  5. O. Hartmann M.D.
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  6. J. P. Armand M.D.
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Additional information

Grant support: This study was supported by grants from the Association pour la Recherche sur le Cancer and Ligue Nationale Française contre le Cancer (Comité des Hautes-Pyrénées).

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Malet-Martino, MC., Martino, R., de Forni, M. et al. Flucytosine conversion to fluorouracil in humans: Does a correlation with gut flora status exist? A report of two cases using fluorine-19 magnetic resonance spectroscopy. Infection 19, 178–180 (1991). https://doi.org/10.1007/BF01643246

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  • DOI: https://doi.org/10.1007/BF01643246

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