Funzela Mechanism of Action

Pharmacology: Pharmacodynamics: Fluconazole, a synthetic broad spectrum bis-triazole antifungal agent, is a highly selective inhibitor of cytochrome P450-dependent enzymes and sterol C-14 alpha-demethylation. These actions result in impairment of ergosterol synthesis in fungal cell membrane, leading to growth inhibition, abnormal cell wall formation, and accumulation of intracellular lipids and membranous vesicles. Depending on the concentration, Fluconazole may be fungicidal or fungistatic.
Antimicrobial Spectrum of Activity: Fluconazole has a relative selectivity for fungal cytochrome P450 system. It exhibits in vitro activity against Cryptococcus neoformans and Candida spp and has demonstrated fungistatic activity in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans. Development of resistance to fluconazole has not been studied; however, there have been reports of cases of superinfection with Candida spp other than Candida albicans, which are often inherently nonsusceptible to fluconazole.
Like other azole antifungal agents, most fungi show a higher apparent sensitivity to fluconazole in vivo than in vitro. Activity has been demonstrated against fungal infections caused by Aspergillus flavus and Aspergillus fumigatus in mice. Fluconazole is active in animal models of endemic mycoses, including one model of Blastomyces dermatitidis pulmonary infections, one model of Coccidioides immitis intracranial infections and several models of Histoplasma capsulatum pulmonary infection.
Coadministration of fluconazole and amphotericin B in infected normal and immunosuppressed mice showed a small additive antifungal effect in systemic infection with Aspergillus fumigatus.
Pharmacokinetics: The pharmacokinetic properties of fluconazole are similar after intravenous or oral administration. Bioavailability of oral fluconazole is >90% in healthy volunteers.
Peak plasma fluconazole concentrations in fasted healthy volunteers occur between 1 and 2 hours with a terminal plasma elimination half-life of 30 hours after oral administration. A single oral 400 mg dose leads to a mean C_max of 6.72 mcg/mL; after single oral doses of 50 to 400 mg, plasma concentrations and AUC are dose-proportional. A single 150 mg oral dose given to 10 lactating women resulted in a mean C_max of 2.61 mcg/mL.
Steady-state concentrations are reached within 5 to 10 days after oral doses of 50 to 400 mg given once daily. Administration of a loading dose (day 1) of twice the usual daily dose results in plasma concentrations close to steady state by day 2. The apparent volume of distribution either single or multiple oral doses for up to 14 days. See Table 1.

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In healthy volunteers, fluconazole is cleared primarily by renal excretion, with 80% of the dose appearing in the urine unchanged, and 11% as metabolites. Fluconazole's pharmacokinetics are markedly affected by reduction in renal function. There is an inverse relationship between elimination half-life and creatinine clearance. Dose may need to be reduced in patients with impaired renal function. A 3 hour hemodialysis session decreases plasma concentrations by 50%.
Doses of 200 to 400 mg once daily for up to 2 weeks in healthy volunteers were associated with small, inconsistent effects on testosterone and endogenous corticosteroid concentrations and the ACTH-stimulated cortisol response.