Fluconazole is a triazole antifungal agent which inhibits fungal cytochrome P450- dependent enzymes resulting in impairment of ergosterol synthesis in fungal cell membranes. Fluconazole is active against Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Epidermophyton spp., Histoplasma capsulatum, Microsporum spp., and Trichophyton spp.
Fluconazole is well absorbed following oral administration achieving a bioavailability of 90% or more. Mean peak plasma concentrations of 6.72mg per mL have been reported in healthy subjects following a 400mg oral dose. Peak concentrations are reached within 1 to 2 hours of oral administration. Multiple dosing leads to increases in peak plasma concentrations; steady-state concentrations are reached in 5 to 10 days but may be attained on day 2 if a loading dose is given. Fluconazole is widely distributed and the apparent volume of distribution is close to that of total body water. Concentrations in breast milk, joint fluid, saliva, sputum, vaginal fluids, and peritoneal fluid are similar to those achieved in plasma. Concentrations in the CSF range from 50 to 90% of plasma concentrations, even in the absence of meningeal inflammation. Protein binding is only about 12%.
About 80% of a dose is excreted unchanged in the urine and about 11% as metabolites. The elimination half-life of fluconazole is about 30 hours and is increased in patients with renal impairment. Fluconazole is removed by dialysis.
Diconazol® is used for superficial mucosal candidiasis (oropharyngeal, oesophageal, or vaginal) and for fungal skin infections. It is also given for systemic infections including systemic candidiasis, coccidioidomycosis and cryptococcosis. Its use in the treatment of acute cryptococcosis meningitis has gained a lot of importance in the management of opportunistic infections in HIV/AIDS patients.
DOSAGE AND ADMINISTRATION:
- Superficial mucosal candidiasis:
- Oropharyngeal candidiasis:50 – 100mg daily treatment for 7 to 14 days.
- Atrophic oral candidiasis associated with dentures:50 – 100mg daily treatment 14 days.
- Other mucosal candidiasis: e.g. oesophagitis 50 – 100mg daily treatment for 14 to 30 days.