A water-soluble, phosphate prodrug of fluconazole, a triazole antifungal agent and 14-alpha demethylase inhibitor used in the treatment and prevention of superficial and systemic fungal infections.Fungal Infection Approved(In Vitro):To investigate the polarized bioconversion and the Transwell transport of phosphate prodrugs in Caco-2 monolayer, 10 μM Fosfluconazole or Fosphenytoin is dosed either in the apical or basal compartment in Transwell plates. Both prodrugs are efficiently cleaved in the apical compartment after a 2 h incubation. To further investigate the kinetics of ALP-mediated bioconversion, the concentration-dependent ALP-mediated bioconversions are conducted to determine the Michaelis-Menten constant (Km) of prodrug bioconversion in Caco-2 monolayers. The saturation curves of Fosphenytoin and Fosfluconazole with the concentration increase are found. The estimated Km values of Fosphenytoin and Fosfluconazole are 1160 and 357 μM, respectively.\n(In Vivo):The apparent half-life for Fosfluconazole bioconversion in intestinal mucosa scraps is 10 min. Fluconazole (FLCZ) is an antifungal agent that is efficacious in the treatment of fungal peritonitis. Fosfluconazole (F-FLCZ) is the phosphate prodrug of FLCZ, which is highly soluble compared with FLCZ. F-FLCZ is useful against fungal peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients because it has a high water solubility. The aims of the present study are to characterize the peritoneal permeability of FLCZ and the pharmacokinetics of FLCZ and F-FLCZ after intraperitoneal (i.p.) administration to peritoneal dialysis rats. FLCZ or F-FLCZ is administered intravenously and intraperitoneally. After the i.p. administration of F-FLCZ, FLCZ is detected in circulating blood and the dialyzing fluid in peritoneal dialysis rats. The concentration of plasma FLCZ after the i.p. F-FLCZ administration is lower than that after the intravenous (i.v.) F-FLCZ administration. It is considered that the dose should be increased appropriately when F-FLCZ is administered intraperitoneally. The profiles of plasma FLCZ after i.v. and i.p. administrations are analyzed using a two-compartment model in which the distribution volume of the peripheral compartment is fixed at a volume of the dialyzing fluid (peritoneal dialysis PK model). The peritoneal dialysis PK model could describe the profiles of plasma and dialyzing fluid FLCZ. These results suggest that FLCZ and F-FLCZ could be administered intraperitoneally for the treatment of fungal peritonitis in CAPD patients.
Research Area
Pharmacology & Drug Discovery
Images & Validation
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Key Properties
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CAS Number
194798-83-9
MW
386.2507
Purity
>98% (HPLC)
Formula
C13H13F2N6O4P
SMILES
c1cc(c(cc1F)F)C(Cn2cncn2)(Cn3cncn3)OP(=O)(O)O
Target
Fungal
Solubility
DMSO: 6.2 mg/mL (Need ultrasonic and warming)
Bioactivity
−
In Vivo
The apparent half-life for Fosfluconazole bioconversion in intestinal mucosa scraps is 10 min. Fluconazole (FLCZ) is an antifungal agent that is efficacious in the treatment of fungal peritonitis. Fosfluconazole (F-FLCZ) is the phosphate prodrug of FLCZ, which is highly soluble compared with FLCZ. F-FLCZ is useful against fungal peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients because it has a high water solubility. The aims of the present study are to characterize the peritoneal permeability of FLCZ and the pharmacokinetics of FLCZ and F-FLCZ after intraperitoneal (i.p.) administration to peritoneal dialysis rats. FLCZ or F-FLCZ is administered intravenously and intraperitoneally. After the i.p. administration of F-FLCZ, FLCZ is detected in circulating blood and the dialyzing fluid in peritoneal dialysis rats. The concentration of plasma FLCZ after the i.p. F-FLCZ administration is lower than that after the intravenous (i. v.) F-FLCZ administration. It is considered that the dose should be increased appropriately when F-FLCZ is administered intraperitoneally. The profiles of plasma FLCZ after i. v. and i.p. administrations are analyzed using a two-compartment model in which the distribution volume of the peripheral compartment is fixed at a volume of the dialyzing fluid (peritoneal dialysis PK model). The peritoneal dialysis PK model could describe the profiles of plasma and dialyzing fluid FLCZ. These results suggest that FLCZ and F-FLCZ could be administered intraperitoneally for the treatment of fungal peritonitis in CAPD patients.
In Vitro
To investigate the polarized bioconversion and the Transwell transport of phosphate prodrugs in Caco-2 monolayer, 10 μM Fosfluconazole or Fosphenytoin is dosed either in the apical or basal compartment in Transwell plates. Both prodrugs are efficiently cleaved in the apical compartment after a 2 h incubation. To further investigate the kinetics of ALP-mediated bioconversion, the concentration-dependent ALP-mediated bioconversions are conducted to determine the Michaelis-Menten constant (Km) of prodrug bioconversion in Caco-2 monolayers. The saturation curves of Fosphenytoin and Fosfluconazole with the concentration increase are found. The estimated Km values of Fos phenytoin and Fos fluconazole are 1160 and 357 μM, respectively.
Storage & Handling
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Storage
Storage temperature: -20°C. Stability: ≥ 2 years
Expiration Date
12 months from date of receipt.
Disclaimer
For research use only
Alternative Names
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Fosfluconazole | Fosfluconazole, Procif | UK 292663 | UK-292,663
10 mg, 25 mg, 50 mg, 100 mg, 200 mg, 5 mg, 1 ml x 10 mM (in DMSO)
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