Triazole antifungals

Group of antimycotics that inhibit the ergosterol synthesis of fungal cells. This leads to a fungistatic effect. The characteristic feature of triazoles is the five-membered heterocyclic ring with 3N atoms, which is complexly substituted.

The following preparations are important for human therapy:

• Fluconazole: Fluconazole has a good effect against almost all fungi, except Candida krusei and partly Candida glabrata. Also dermatophytes are usually quite sensitive, but there are weaknesses against moulds. Because of its good pharmacological properties (administration orally or parenterally, excellent tissue mobility, excellent tolerability) it has become a basic therapeutic agent in therapy as well as prophylaxis of fungal infections. Fluconazole is mainly renal excreted.
• itraconazole: Itraconazole has a comparatively broader spectrum than Fluconazole, whereby above all the better effect against some molds is to be emphasized. However, the strongly lipophilic preparation is hardly intestinally absorbed, it must first be dissolved in a carrier, the cyclodextrin. In this way it can be applied parenterally.
• Voriconazole: Voriconazole is the triazole with the broadest spectrum of activity. Also fungi of the genera Fusarium and Zygomycetes, in the spectrum of this azole antifungal. It can be administered orally or i.v. (incorporated in cyclodextrin). It is playing an increasing role in the prophylaxis of fungal infections of seriously ill patients.
• Posaconazole: Posaconazole has been approved for adults in Germany since October 2005. Posaconazole is considered an antimycotic which is used for severe fungal infections or for those resistant to itraconazole or amphotericin B, especially in immunocompromised patients. Posaconazole inhibits the ergosterol biosynthesis and here a fungus-specific cytochrome P450 isoenzyme (CYP51A1), which is responsible for the conversion of lanosterol into ergosterol. Ergosterol precursors are incorporated into the membrane and the permeability for cell components is increased. Posaconazole is highly lipophilic and is almost exclusively metabolized. 65% of the oral dose is excreted unchanged in the gut.
• Isavuconazole: Triazole antifungal drug for the treatment of invasive aspergillosis or mucor mycosis in patients in whom, treatment with Amphotericin B is not appropriate.

Especially the triazoles have considerably better therapeutic properties compared to the imidazole antifungals due to their higher affinity to the fungal enzyme. The metabolic elimination of the triazoles takes place to a varying extent via CYeP3A4, CYP2C9/2C19 or glucoroinidation (the latter applies especially to posoconazole). Triazoles also act as inhibitors of CYP enzymes and therefore have a high interaction potential.