Evidence for conversion of 5-fluorocytosine to 5-fluorouracil in humans: possible factor in 5-fluorocytosine clinical toxicity

R. B. Diasio, D. E. Lakings, J. E. Bennett

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

A gas chromatographic-mass spectrometric method for detecting 5-fluorouracil (5-FU) in serum at concentrations as low as 10 ng/ml was used to determine to what extent 5-FU was present in the serum of patients taking oral 5-fluorocytosine (5-FC). Preliminary studies in two patients and two healthy volunteers given an initial 2-g oral dose of 5-FC demonstrated sustained serum 5-FU levels (>100 ng/ml during the 5 h after ingestion of drug. Pharmaceutical preparations of 5-FC used in these studies were shown to be insignificantly contaminated with 5-FU (<0.03%), suggesting in vivo conversion of 5-FC to 5-FU had occurred. Serum samples from seven patients with cryptococcal meningitis treated with amphotericin B and 5-FC were examined for 5-FU. Five of these patients had experienced hematological or other toxicity attributed to 5-FC at some time during the course of therapy. Of 41 serum samples, 20 were observed to have 5-FU levels greater than 1,000 ng/ml in the range observed with cancer chemotherapeutic doses of 5-FU known to be associated with hematological toxicity. It is concluded that conversion of 5-FC to 5-FU occurs in humans and furthermore that 5-FU may account for some of the toxicity observed with 5-FC.

Original languageEnglish (US)
Pages (from-to)903-908
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume14
Issue number6
DOIs
StatePublished - Jan 1 1978

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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