Biozole Mechanism of Action

Pharmacology: Pharmacodynamics: Fluconazole, a triazole antifungal agent, is a potent and specific inhibitor of fungal sterol synthesis. Both orally and intravenously administered fluconazole was active in a variety of animal fungal infection models. Activity has been demonstrated against opportunistic mycoses, such as infections with Candida spp, including systemic candidiasis in immunocompromised animals; with Cryptococcus neoformans, including intracranial infections; with Microsporum spp; and with Trichophyton spp. Fluconazole has also been shown to be active in animal models of endemic mycoses, including infections with Blastomyces dermatitidis, with Coccidioides immitis, including intracranial infection; and with Histoplasma capsulatum in normal and immunosuppressed animals.
Pharmacokinetics: The pharmacokinetic properties of fluconazole are similar following IV or oral administration. After oral administration fluconazole is well absorbed, and systemic bioavailability exceeds 90% compared with intravenous administration. Oral absorption is not affected by concomitant food intake. Peak plasma concentrations of the drug generally are attained within 1-2 hours with a terminal plasma elimination half-life of approximately 30 hours after administration. Plasma concentrations are proportional to dose. Administration of loading dose (on day 1) of twice the usual daily dose results in plasma levels close to steady-state by the second day. The apparent volume of distribution approximates to total body water. Plasma protein binding is low (11-12%).
Fluconazole achieves good penetration in all body fluids studied. The levels of fluconazole in saliva and sputum are similar to plasma levels. In patients with fungal meningitis, fluconazole levels in the CSF are approximately 80% the corresponding plasma levels. The major route of excretion is renal, with approximately 80% of the administered dose appearing in the urine as unchanged drug. About 11% of the dose is excreted in the urine as metabolites. Fluconazole clearance is proportional to creatinine clearance.