Document Detail


An in vitro study on the active conversion of flucytosine to fluorouracil by microorganisms in the human intestinal microflora.
MedLine Citation:
PMID:  12714804     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. CONCLUSION: 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:
András Vermes; Ed J Kuijper; Henk-Jan Guchelaar; Jacob Dankert
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Chemotherapy     Volume:  49     ISSN:  0009-3157     ISO Abbreviation:  Chemotherapy     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-04-25     Completed Date:  2003-12-08     Revised Date:  2009-11-11    
Medline Journal Info:
Nlm Unique ID:  0144731     Medline TA:  Chemotherapy     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  17-23     Citation Subset:  IM    
Copyright Information:
Copyright 2003 S. Karger AG, Basel
Affiliation:
Department of Clinical Pharmacy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.vermes@erasmusmc.nl
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MeSH Terms
Descriptor/Qualifier:
Antifungal Agents / adverse effects,  metabolism*
Child
Dose-Response Relationship, Drug
Escherichia coli / drug effects,  metabolism*
Feces / microbiology
Female
Flucytosine / adverse effects,  metabolism*
Fluorouracil / adverse effects,  metabolism*
Humans
Intestines / microbiology*
Male
Middle Aged
Neutropenia / chemically induced
Chemical
Reg. No./Substance:
0/Antifungal Agents; 2022-85-7/Flucytosine; 51-21-8/Fluorouracil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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