Flucytosine

Male Sprague-Dawley rats

Clinical trail completed in evaluating the effectiveness and safety of Amphotericin B plus Flucytosine (5-Fluorocytosine) compared to Amphotericin B alone for a first episode of acute cryptococcal meningitis in AIDS patients, and comparing the effectiveness and safety of Fluconazole versus Itraconazole.

Flucytosine (5-Fluorocytosine, 5-FC, Ancobon) is an antifungal drug with IC50 of 0.12 ug/mL in C. albicans.

Flucytosine is first synthesized in 1957 but its antifungal properties discovered in 1964.

0.12 ug/mL [1], 0.12 ug/mL [1], 0.12 ug/mL [1], 0.12 ug/mL [1], 0.12 ug/mL [1], 0.12 ug/mL [1]

Administration of Flucytosine in combination with monoclonal antibody 2H1 to A/JCr mice infected with C. neoformans significantly reduces lung but not brain cfu, which is more effective than either agent alone. [2] The combination of intravenous Flucytosine in 0.9% saline (NaCl) and amphotericin B (AmB) provides synergistic antifungal activity and is associated with a lower incidence of nephrotoxicity than with AmB treatment alone. Infusion of Flucytosine (5-10 mg/kg/min) dissolved in 5% glucose into the renal artery of an in situ perfused kidney for 15 minutes increases renal blood flow (RBF) in the rat, and the renal vasodilatation persists for the duration of the Flucytosine infusion, with a maximal increase of 2.5+/-0.7 mL/min. [4]

Microdilution method, The culture media used are RPMI 1640 with glutamine, without bicarbonate and phenol red, buffered with morpholinopropanesulfonic acid (MOPS) (0.165 M, pH 7.0). Two-fold serial dilutions of Flucytosine (0.06-64 ug/mL) are prepared and dispensed in 50 uL aliquot, in flat-bottom 96-well assay plates which are kept frozen at -70 C in sealed plastic bags until used. The inoculum is prepared spectrophotometrically and standardized to a concentration of 1.0-5.0, 103 cfu per mL. A 50 uL volume of this suspension is used to inoculate each well containing 50 uL of the double concentration of Flucytosine to be tested. Once inoculated, each well therefore contains 100 uL of broth favoured over 200 uL to facilitate the agitation of the plates prior to spectrophotometric reading. After an incubation period of 24 and 48 hours at 35 C, the plates are agitated for 3 minutes at 900 r.p.m. with a shaker and the optical density of the growth in each well is determined with the use of an automatic plate reader set at 495 nm. The inhibitory concentration of IC50 is computed mathematically.

129, 09

DMSO 8 mg/mL, Water 5 mg/mL, Ethanol <1 mg/mL