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5‐fluorocytosine‐related bone‐marrow depression and conversion to fluorouracil: a pilot study
Author(s) -
Vermes András,
Guchelaar HenkJan,
Van Kuilenburg Andre B.P.,
Dankert Jacob
Publication year - 2002
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1046/j.1472-8206.2002.00064.x
Subject(s) - platelet , medicine , toxicity , bone marrow , fluorouracil , gastroenterology , depression (economics) , pharmacokinetics , pharmacology , chemotherapy , immunology , economics , macroeconomics
The aim of this study is to investigate whether fluorouracil (5‐FU) could be responsible for bone‐marrow depression occurring in fluorocytosine (5‐FC) treated patients. Six 5‐FC treated patients were included in this pilot study. Toxicity was monitored by means of thrombocyte and leucocyte counts. 5‐FC and 5‐FU serum levels were measured using a high‐performance liquid chromatography (HPLC) assay that allows simultaneous determination of both compounds. The amounts of 5‐FU in the 34 available serum samples remained below the limit of quantitation (< 0.05 mg/L), whereas 5‐FC levels could be detected in all samples. Instead, low levels of the 5‐FU catabolite α ‐fluoro‐ β ‐alanine (FBAL) were detected in several of the investigated serum samples. In case of three patients thrombocyte counts remained within the normal range during 5‐FC treatment, whereas one patient developed thrombocytopenia (50 × 10 9 thrombocytes/L) during therapy. Furthermore, one patient developed leucocytopenia (2.6 × 10 9 leucocytes/L) during 5‐FC therapy, whereas the remaining five patients were suffering from leucocytosis prior to 5‐FC therapy. In conclusion, we found nondetectable 5‐FU serum concentrations (< 0.05 mg/L) in ICU patients treated with intravenous 5‐FC, making it unlikely that 5‐FC‐associated toxicity results from 5‐FU exposure in patients receiving intravenous 5‐FC therapy. These findings may be explained by the fact that our patients received 5‐FC intravenously instead of orally, therefore not allowing active conversion of 5‐FC to 5‐FU by the human intestinal microflora.