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Azole antifungals: 35 years of invasive fungal infection management

David Allen1, Dustin Wilson, Richard Drew

  • 1Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA.

Expert Review of Anti-Infective Therapy
|April 7, 2015
PubMed

Insights

The development of azole antifungal drugs has evolved significantly, offering improved treatments for fungal infections with better safety and efficacy profiles over time. Newer azoles in development promise even more predictable pharmacokinetics and fewer side effects.

Area of Science:

  • Medical Mycology
  • Pharmacology
  • Infectious Diseases

Background:

  • Limited and toxic treatment options for invasive fungal infections existed before 1981.
  • Ketoconazole represented an initial advancement, but was superseded by fluconazole and itraconazole due to improved properties.
  • Subsequent triazoles like posaconazole and voriconazole expanded spectrum, particularly against molds.

Purpose of the Study:

  • To review the historical development and advancements in azole antifungal therapies.
  • To highlight the pharmacokinetic and safety challenges associated with existing triazoles.
  • To introduce emerging azole agents with improved therapeutic potential.

Main Methods:

  • Literature review of antifungal drug development.
  • Comparative analysis of azole antifungal agents based on spectrum, pharmacokinetics, and safety.
  • Discussion of current trends and future directions in azole antifungal research.

Main Results:

  • Ketoconazole offered initial improvements but had limitations.
  • Fluconazole, itraconazole, posaconazole, and voriconazole demonstrated progressive enhancements in spectrum and efficacy.
  • Existing triazoles exhibit significant pharmacokinetic variability and drug interactions, except for fluconazole.

Conclusions:

  • The evolution of azoles has led to more effective treatments for fungal infections.
  • Pharmacokinetic variability and drug interactions remain challenges for current triazoles.
  • Next-generation azoles are expected to offer superior pharmacokinetic profiles and safety, building upon the efficacy of existing agents.
Keywords:
albaconazoleantifungalsazoleisavuconazoleravuconazole

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