title: Evidence for conversion of 5-fluorocytosine to 5-fluorouracil in humans: possible factor in 5-fluorocytosine clinical toxicity.
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.
mesh_terms: D002214:Capsules; D003453:Cryptococcosis / Q000188:drug therapy / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives*; D005437:Flucytosine / Q000009:adverse effects / Q000378:metabolism*; D005472:Fluorouracil / Q000009:adverse effects / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008581:Meningitis / Q000188:drug therapy / Q000378:metabolism
chemical_list: D002214:Capsules; D003596:Cytosine; D005437:Flucytosine; D005472:Fluorouracil