Mycozole/Mycozole IV Mechanism of Action

Pharmacology: Pharmacokinetics: Fluconazole is well absorbed after oral doses, bioavailability from the oral route being 90% or more of that from the intravenous route. Peak concentrations are reached within one to two hours of oral administration. Plasma concentrations are proportional to the dose over a range of 50 to 400 mg. Multiple dosing leads to increase 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 cerebrospinal fluid range from 50 to 90% of plasma concentrations, even in the absences 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.
Distribution: Salivary concentrations of fluconazole after oral doses should be adequate for the treatment of oropharyngeal and esophageal candidiasis even in patients with AIDS who may have decreased salivation. Treatment failures are more likely to be due to inadequate dosage or resistant organisms than to decreased salivary secretion.
Pharmacologically active concentrations of fluconazole have been detected in scalp hair and nails after oral treatment with conventional daily doses and with once-weekly administration.
Microbiology: Antimicrobial Action: Fluconazole is a triazole antifungal drug wherein sensitive fungi inhibits cytochrome P450-dependent enzymes, resulting in impairment of ergosterol synthesis in fungal cell membranes. It is active against Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Epidermophyton spp., Histoplasma capsulatum, Microsporum spp., and Trichophyton spp.
Resistance has developed in some Candida spp. following long-term prophylaxis with fluconazole, and cross-resistance with other azoles has been reported.
Resistance: The emergence of strains of Candida species resistant to fluconazole has become increasingly important, particularly in immunocompromised patients receiving long-term prophylaxis with fluconazole. In addition to resistance in C. albicans, infections with C. dubliniensis, C. glabrata, and C. krusei, all of which may be less sensitive to fluconazole than C. albicans, have been noted in these patients, and secondary resistance of C. glabrata has been reported during fluconazole therapy. Resistance to fluconazole has been reported to occur more frequently than resistance to either ketoconazole or itraconazole and may be related to the widespread use of this drug. Cross-resistance with other azoles and with amphotericin B has been reported.
Fluconazole resistance has also been reported in Cryptococcus neoformans and Histoplasma capsulatum. Histoplasmosis developed during treatment with fluconazole in a patient with HIV infection. Fluconazole-resistant C. neoformans has been isolated from an immunocompetent patient who had not been exposed to azole antifungals previously.