Fungazol Mechanism of Action

Pharmacotherapeutic classification: Antimycotics for systemic use, imidazole derivatives.
PHARMACOLOGY: Pharmacodynamics: Ketoconazole is a synthetic imidazole derivative with a fungicidal (normal concentrations) or fungistatic activity (high concentrations) in in-vitro studies.
Ketoconazole is active against clinical infection with Blastomyces dermatitidis, Candida sp., Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis and Phialophora sp. Ketoconazole is also active against Trichophyton sp., Epidermophyton sp., and Microsporum sp. Ketoconazole is also active in vitro against a variety of fungi and yeast.
Ketoconazole inhibits the biosynthesis of ergosterol in fungi and changes the composition of other lipid components in the membrane.
Pharmacokinetics: Absorption: Ketoconazole is a weak dibasic agent and thus requires acidity for dissolution and absorption. Mean peak plasma levels of approximately 3.5 μg/ml are reached within 1 to 2 hours, following oral administration of a single 200 mg dose taken with a meal.
Distribution: In vitro, the plasma protein binding is about 99% mainly to the albumin fraction. Only a negligible proportion of ketoconazole reaches the cerebral-spinal fluid.
Metabolism: Following absorption from the gastrointestinal tract, ketoconazole is converted into several inactive metabolites. The major identified metabolic pathways are oxidation and degradation of the imidazole and piperazine rings, oxidative O-dealkylation and aromatic hydroxylation.
Excretion: About 13% of the dose is excreted in the urine, of which 2 to 4% is unchanged drug. The major route of excretion is through the bile into the intestinal tract. Subsequent plasma elimination is biphasic with a half-life of 2 hours during the first 10 hours and 8 hours thereafter.