Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1978 Dec;14(6):903–908. doi: 10.1128/aac.14.6.903

Evidence for Conversion of 5-Fluorocytosine to 5-Fluorouracil in Humans: Possible Factor in 5-Fluorocytosine Clinical Toxicity

Robert B Diasio 1, Duane E Lakings 2, John E Bennett 3
PMCID: PMC352577  PMID: 742878

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.

Full text

PDF
903

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennet J. E. Flucytosine. Ann Intern Med. 1977 Mar;86(3):319–321. doi: 10.7326/0003-4819-86-3-319. [DOI] [PubMed] [Google Scholar]
  2. Block E. R., Bennett J. E. Pharmacological studies with 5-fluorocytosine. Antimicrob Agents Chemother. 1972 Jun;1(6):476–482. doi: 10.1128/aac.1.6.476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Finj C., Sadée W. Determination of 5-fluorouracil (NSC-19893) plasma levels in rats and man by isotope dilution-mass fragmentography. Cancer Chemother Rep. 1975 Mar-Apr;59(2 Pt 1):279–286. [PubMed] [Google Scholar]
  4. Hillcoat B. L., Kawai M., McCulloch P. B., Rosenfeld J., Williams C. K. A sensitive assay of 5-fluorouracil in plasma by gas chromatography-mass spectrometry. Br J Clin Pharmacol. 1976 Feb;3(1):135–143. doi: 10.1111/j.1365-2125.1976.tb00580.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kauffman C. A., Frame P. T. Bone marrow toxicity associated with 5-fluorocytosine therapy. Antimicrob Agents Chemother. 1977 Feb;11(2):244–247. doi: 10.1128/aac.11.2.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Koechlin B. A., Rubio F., Palmer S., Gabriel T., Duschinsky R. The metabolism of 5-fluorocytosine-2-14-C and of cytosine-14-C in the rat and the disposition of 5-fluorocytosine-2-14-C in man. Biochem Pharmacol. 1966 Apr;15(4):435–446. doi: 10.1016/0006-2952(66)90254-1. [DOI] [PubMed] [Google Scholar]
  7. Lakings D. B., Adamson R. H. Quantitative analysis of 5-fluorouracil in human serum by selected ion monitoring gas chromatography--mass spectrometry. J Chromatogr. 1978 Nov 1;146(3):512–517. doi: 10.1016/s0378-4347(00)81214-1. [DOI] [PubMed] [Google Scholar]
  8. O'Donovan G. A., Neuhard J. Pyrimidine metabolism in microorganisms. Bacteriol Rev. 1970 Sep;34(3):278–343. doi: 10.1128/br.34.3.278-343.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Polak A., Eschenhof E., Fernex M., Scholer H. J. Metabolic studies with 5-fluorocytosine-6-14C in mouse, rat, rabbit, dog and man. Chemotherapy. 1976;22(3-4):137–153. doi: 10.1159/000221923. [DOI] [PubMed] [Google Scholar]
  10. Wade D. N., Sudlow G. The kinetics of 5-fluorocytosine elimination in man. Aust N Z J Med. 1972 May;2(2):153–158. doi: 10.1111/j.1445-5994.1972.tb03925.x. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES