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Flucytosine

Flucytosine, a fluorinated pyrimidine analogue, is a synthetic antimycotic drug. Chemically it is referred to as 4-amino-5-fluoro-2(1H)-pyrimidinon. The sum formula is C4H4FN3O. Fucytosine has the CAS-Number 2022-85-7. It is structurally related to the cytostatic flourouracil and to floxuridine. It is available in oral and in some countries also in injectable form. A common brand name is Ancobon®. The drug is dispensed in capsules of 250 mg and 500 mg strength. The injectable form is diluted in 250ml NaCl-solution to contain 2.5 grams totally (10mg per ml). more...

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The solution is physically incompatible with other drugs including Amphotericin B.

Pharmacology

Mechanisms of action

Two major mechanisms of acton have been elucidated, one is that the drug is intrafungally converted into the cytostatic flourouracil that undergoes further steps of activation and finally interacts as 5-fluorouridinetriphosphate with RNA-biosynthesis and disturbs therefore the building of certain essential proteins. The other mechanism is the conversion into 5-flourodeoxyuridinemonophosphate which inhibits fungal DNA-synthesis.

Spectrum of susceptible fungi and Resistance

Flucytosine is as well in vitro and in vivo active against some strains of Candida and Cryptococcus. Limited studies demonstrate that Flucytosine may be of value against infections with Sporothrix, Aspergillus, Cladosporium, Exophila, and Phialophora. Resistance is quite commonly seen as well in treatment naive patients and under current treatment with Flucytosine. In different strains of Candida resistance has been noted to occur in 1 to 50% of all specimen obtained from patients.

Pharmacokinetic data

Flucytosine is well absorbed (75 to 90%) from the GI-Tract. Intake with meals slows the resorption, but does not decrease the amount resorbed. Following an oral dose of 2 grams peak serum levels are reached after approximately 6 hours. The time to peak level decreases with continued therapy. After 4 days peak levels are measured after 2 hours. The drug is eliminated renally. In normal patients Flucytosine has reportedly a half-life of 2.5 to 6 hours. In patients with impared renal function higher serum levels are seen and the drug tends to cumulate in these patients. The drug is mainly excreted unchanged in the urine (90% of an oral dose) and only traces are metabolized and excreted in the feces. Therapeutic serum levels range from 25 to 100mcg/ml. Serum levels in exceed of 100mcg are associated with a higher incidence of side-effects. Periodic measurements of serum levels are recommended for all patients and are a must in patients with renal damage.

Human overdose

Symptoms and their severities are unknown, because Flucytosine is used under close medical supervision, but expected to be an excess of the usually encountered side-effects on bone-marrow, GI-Tract, liver, and kidney-function. Vigouros hydration and hemodialysis may be helpful to remove the drug from the body. Hemodialysis is particular useful in patients with impaired renal function.

Human carcinogenity

It is not known, if Flucytosine is a human carcinogen. The issue has been raised because traces of 5-fluorouracil, which is a known carcinogen, are found in the colon resulting from the metabolization of Flucytosine.

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Successful Treatment of Cryptococcal Osteomyelitis and Paraspinous Abscess With Fluconazole and Flucytosine. : An article from: Southern Medical Journal $5.95

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