Tozene Mechanism of Action

Pharmacology: Pharmacodynamics: Flucytosine, a fluorinated pyrimidine analog, is a synthetic antifungal agent. Two possible mechanisms of action have been identified for Flucytosine. Flucytosine appears to enter fungal cells via the action of fungal-specific cytosine permease. Inside the cell, Flucytosine is converted into fluorouracil (5-FU) by cytosine deaminase and then after several intermediate steps is converted into 5-fluorouridine triphosphate (FUTP). FUTP is incorporated into fungal RNA and interferes with protein synthesis. Flucytosine also appears to be converted to 5-fluorodeoxyuridine monophosphate, which noncompetitively inhibits thymidylate synthetase and interferes with DNA synthesis. Flucytosine does not appear to have antineoplastic activity. Flucytosine has been demonstrated to be effective against the following organisms: Aspergillus spp. (rare strains), Candida spp., Cryptococcus spp., Torulopsis glabrata (Candida glabrata).
Pharmacokinetics: Absorption: Flucytosine is absorbed rapidly and almost completely from the gastrointestinal tract (GI). Bioavailability is 78-89% following oral administration.
Distribution: Flucytosine is widely distributed into body tissues and fluids including liver, kidney, spleen, heart, aqueous humor and bronchial secretions. Flucytosine is distributed into cerebrospinal fluid (CSF) following oral administration. CSF concentrations are approximately 65-90% of serum levels. About 2-4% of Flucytosine is protein bound.
Metabolism: A small amount of Flucytosine may be metabolized to fluorouracil.
Elimination: More than 90% of the dose is excreted unchanged in the urine by glomerular filtration. The small amount of an oral dose of Flucytosine not absorbed from the gastrointestinal tract is eliminated unchanged in the feces. The elimination half-life is 2.5-6 hours in the patients with normal renal function but increases with decreasing renal function. Flucytosine is readily removed by peritoneal dialysis or hemodialysis.