Glitzol (For Fungal Infections)

Glitzol (Capsule)

Itraconazole

Only effective Anti Fungal against types of organism, dermatlophytes & moulds.

Pulse therapy has proven efficacy in onychomycosis.

·         Fungal Infection of the nails.

·         Fungal Infection throughout the body (systemic fungal infection)

·         Fungal menigitis

·         Fungal skin infections, eg athletes foot, ringworm, Candida skin infections.

·         Infections of mucosa caused by Candida fungi, eg thrush effecting the mouth or throat.

·         To prevent the fungal infection in patient who have no white blood cells called neutrophils to fight infection (neutropenia)

·         To prevent recurrence of fungal infection in patients with AIDS.

·       Vaginal thrush (candidasis)

Mechanism Of Action

            Itraconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.

Pharmacodynamics

Itraconazole is an imidazole/triazole type antifungal agent. Itraconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Itraconazole exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans.

 Absorption

The absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal.

Volume Of Distribution

796 ± 185 L

Protein Binding

99.8%

Metabolism

Itraconazole is extensively metabolized by the liver into a large number of metabolites, including hydroxy itraconazole, the major metabolite. The main metabolic pathways are oxidative scission of the dioxolane ring, aliphatic oxidation at the 1-methylpropyl substituent, N-dealkylation of this 1-methylpropyl substituent, oxidative degradation of the piperazine ring and triazolone scission.

Route Of Elimination

Itraconazole is metabolized predominately by the cytochrome P450 3A4 isoenzyme system (CYP3A4) in the liver, resulting in the formation of several metabolites, including hydroxy itraconazole, the major metabolite. Fecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is less than 0.03% of the dose. About 40% of the dose is excreted as inactive metabolites in the urine. No single excreted metabolite represents more than 5% of a dose.

Half life

21 hours

Clearance

381 +/- 95 mL/minute [IV administration]

Toxicity

No significant lethality was observed when itraconazole was administered orally to mice and rats at dosage levels of 320 mg/kg or to dogs at 200 mg/kg.

Affected organisms

Fungi, yeast and protozoan’s.