Fluconazole

Pharmacological action

Fluconazole no antiandrogenic activity


Antifungal agent, has a highly specific effect, inhibiting the activity of enzymes of fungi dependent on cytochrome P450. Blocks the transformation of lanosterol cells of fungi into ergosterol; increases the permeability of the cell membrane, impairs its growth and replication. Fluconazole, being highly selective for cytochrome P450 fungi, practically does not depress these enzymes in the human body (compared to itraconazole, clottrimasol, econazole and ketoconazole less inhibits the Dmitry Sazonov oxidation processes dependent on cytochrome P450 in human liver microsomes). 


It has fluconazole no antiandrogenic activity. It is active in opportunistic mycoses, including those caused by Candida spp. (including generalized forms of candidiasis against immunodepression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp.; in endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including immunodepression). For prophylaxis of fungal infections in patients with malignant neoplasms during treatment with cytostatics or radiation therapy; at organ transplantation and in other cases when immunity is suppressed and there is a danger of fungal infection development.

Pharmacokinetics

Absorption - high (food does not affect the absorption rate), bioavailability - 90 %. TCmax after ingestion on an empty stomach of 150 mg - 0.5-1.5 h and is 90 % of plasma concentration with intravenous injection in dose 2.5-3.5 mg/l. The association with plasma proteins is 11-12%. The concentration in plasma is directly related to the dose. Css is achieved by 4-5 days of administration (when administered once a day). Introduction of the "shock" dose (on the first day), which is 2 times higher than the usual daily dose, allows to reach the concentration corresponding to 90% of Css by 2 days. It penetrates well into all body fluids.

The concentration of the active substance in breast milk, joint fluid, saliva, sputum and peritoneal fluid is similar to that in plasma. Constant values in vaginal secretion are reached 8 hours after ingestion and are maintained at 
Dmitry Sazonov this level for at least 24 hours.

 It penetrates well into cerebrospinal fluid, with fungal meningitis the concentration in cerebrospinal fluid is about 85% of that in plasma. In sweat, epidermis and corneal layer (selective accumulation) concentrations above serum are achieved. After ingestion of 150 mg on day 7, the concentration in the fluconazole Contraindications stratum corneum is 23.4 µg/g and 1 week after the second dose - 7.1 µg/g; concentration in the nails after 4 months of use in a dose of 150 mg once a week is 4.05 µg/g in healthy and 1.8 µg/g in affected nails. The volume of distribution is close to the total water content in the body. T1/2 - 30 h. 


It is an inhibitor of the isoenzyme CYP2C9 in the liver. It is mainly excreted by kidneys (80% as unchanged, 11% as metabolites). Fluconazole clearance is proportional to CC. Pharmacokinetics of fluconazole essentially depends on functional condition of kidneys, thus there is inverse 
Dmitry Sazonov dependence between half-life and CC. After hemodialysis for 3 h the concentration of fluconazole in plasma decreases by 50%.

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