From the Guidelines
Itraconazole's mechanism of action involves inhibiting the fungal enzyme 14-alpha-demethylase, disrupting cell membrane integrity, and leading to fungal cell death. This is achieved through its high affinity for fungal cytochrome P450 enzymes, allowing it to target fungal cells while minimizing effects on human cells 1. The drug's effectiveness against a broad spectrum of fungi, including dermatophytes, yeasts, and dimorphic fungi, makes it a valuable treatment option for various fungal infections.
Key Points
- Itraconazole belongs to the triazole class of antifungal medications
- It is effective against a range of fungi, including those causing talaromycosis, as discussed in the global guideline for the diagnosis and management of endemic mycoses 1
- The drug's selective toxicity is due to its higher affinity for fungal cytochrome P450 enzymes than for mammalian ones
- Itraconazole is typically administered orally, with absorption enhanced by food and acidic conditions, and is highly protein-bound in plasma and extensively metabolized in the liver
- Its lipophilic nature allows it to penetrate tissues effectively, including skin, nails, and some body fluids, making it useful for treating various fungal infections, as supported by studies such as the double-blind, placebo-controlled trial in Thailand 1
From the FDA Drug Label
In vitro studies have demonstrated that itraconazole inhibits the cytochrome P450-dependent synthesis of ergosterol, which is a vital component of fungal cell membranes. As with other azoles, itraconazole inhibits the 14C-demethylation step in the synthesis of ergosterol, a cell wall component of fungi.
The mechanism of action of itraconazole is the inhibition of the cytochrome P450-dependent synthesis of ergosterol, a vital component of fungal cell membranes, by inhibiting the 14C-demethylation step in the synthesis of ergosterol 2.
From the Research
Mechanism of Action of Itraconazole
- Itraconazole acts primarily by impairing the synthesis of ergosterol, resulting in a defective fungal cell membrane with altered permeability and function 3.
- The azoles, including itraconazole, inhibit the 14α-sterol-demethylase enzyme, preventing the binding of ergosterol and altering the functionality and structure of the fungal cell wall 4.
- This mechanism of action is effective against a wide variety of mycotic infections, including those caused by Aspergillus species, Candida species, and Cryptococcus species 3, 4.
Spectrum of Activity
- Itraconazole has a broad spectrum of in vitro activity, making it effective against a wide range of fungal infections, including systemic and superficial infections 3.
- It is particularly effective against Aspergillus species, which are often resistant to other antifungal agents 3, 5.
- Itraconazole is also effective against other fungal pathogens, including Candida species, Cryptococcus species, and endemic fungi such as Histoplasma and Coccidioides 4, 6.
Clinical Use
- Itraconazole is widely used for the prevention and treatment of fungal infections, including invasive and allergic fungal infections 6.
- It is available in both oral and intravenous forms, making it practical for long-term use in chronic mycoses 6.
- Itraconazole is also used for the treatment of endemic fungal infections, and its pharmacokinetic variability and potential drug interactions make therapeutic drug monitoring an important consideration 6, 7.