Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions

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ID: 305994
2000
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Abstract
Flucytosine (5-FC) is a synthetic antimycotic compound, first synthesized in 1957. It has no intrinsic antifungal capacity, but after it has been taken up by susceptible fungal cells, it is converted into 5-fluorouracil (5-FU), which is further converted to metabolites that inhibit fungal RNA and DNA synthesis. Monotherapy with 5-FC is limited because of the frequent development of resistance. In combination with amphotericin B, 5-FC can be used to treat severe systemic mycoses, such as cryptococcosis, candidosis, chromoblastomycosis and aspergillosis. Recently, 5-FC has been combined with newer azole antifungal agents; it also plays an important role in a new approach to the treatment of cancer. The severe side effects of 5-FC include hepatotoxicity and bone-marrow depression. In most patients, these side effects are concentration dependent, predictable, possibly avoidable with close monitoring to maintain 5-FC concentrations at <100 mg/L, and reversible with drug discontinuation or reduction of dose. 5-FC is well absorbed after oral administration, penetrates into body tissues well and is excreted mainly by the kidneys. In renal failure, major dose adjustments have to be made. The most important drug interaction of 5-FC occurs with concomitant administration of 5-FC and nephrotoxic drugs, especially amphotericin B. Owing to the crucial role of glomerular filtration in 5-FC elimination, drugs that impair this mechanism will decrease the elimination of 5-FC and thus prolong its half-life.
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Authors András Vermes
Journal The Journal of antimicrobial chemotherapy
Year 2000
DOI
10.1093/jac/46.2.171
URL
https://academic.oup.com/jac/article-pdf/46/2/171/9841241/171.pdf
Keywords Keywords not found

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