title: An in vitro study on the active conversion of flucytosine to fluorouracil by microorganisms in the human intestinal microflora.
abstract: BACKGROUND
  Investigation of the rate of active conversion of flucytosine to fluorouracil by microorganisms in the intestinal microflora.
  
  
  METHODS
  Active conversion of flucytosine was investigated using viable and nonviable Escherichia coli at different flucytosine concentrations. Additionally, flucytosine conversion was studied in fecal specimens from 3 neutropenic patients at the start of the antimicrobial/antifungal prophylaxis (C/A regimen) and 1 week later.
  
  
  RESULTS
  Flucytosine levels decreased by an average of 72, 71 and 72% flucytosine after incubation for 48 h of 10(10) viable E. coli /ml suspension in broth containing 13, 130 and 1300 mg/l flucytosine, respectively. The decreasing flucytosine levels corresponded approximately to an identical increase in fluorouracil levels. Also, a 44% decrease of flucytosine levels occurred when nonviable E. coli were used, indicating that bacterial viability is not necessary for this conversion. When fecal specimens of 2 patients were investigated prior to the C/A regimen, significant flucytosine conversion occurred, whereas this conversion was not observed in the corresponding fecal specimens after 1 week of C/A regimen.
  
  
  CONCLUSIONS
  These in vitro experiments showed that extensive flucytosine conversion can occur in the human intestinal microflora by E. coli. Consequently, fluorouracil exposure and fluorouracil-related toxicity may occur in the flucytosine-treated patient.
authors.affiliation: Department of Clinical Pharmacy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.vermes@erasmusmc.nl
authors.forename: András
authors.initials: A
authors.lastname: Vermes
authors.forename: Ed J
authors.initials: EJ
authors.lastname: Kuijper
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
authors.forename: Jacob
authors.initials: J
authors.lastname: Dankert
mesh_terms: D000935:Antifungal Agents / Q000009:adverse effects / Q000378:metabolism*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D005243:Feces / Q000382:microbiology; D005260:Female; D005437:Flucytosine / Q000009:adverse effects / Q000378:metabolism*; D005472:Fluorouracil / Q000009:adverse effects / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced
chemical_list: D000935:Antifungal Agents; D005437:Flucytosine; D005472:Fluorouracil