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Pharmacokinetics of Azole Antifungals in Cystic Fibrosis

Ryan M Rivosecchi1,2, Palash Samanta3, Moses Demehin4,5

  • 1Department of Pharmacy, UPMC Presbyterian Hospital, Pittsburgh, PA, USA. rivosecchirm@upmc.edu.

Mycopathologia
|August 11, 2017
PubMed

Insights

Cystic fibrosis (CF) patients experience variable antifungal triazole levels due to altered pharmacokinetics. Therapeutic drug monitoring is crucial to prevent treatment failure or toxicity in CF patients with fungal infections.

Area of Science:

  • Medical Mycology
  • Pharmacokinetics
  • Cystic Fibrosis Research

Background:

  • Mucociliary dysfunction in cystic fibrosis (CF) increases susceptibility to fungal infections, particularly Aspergillus fumigatus.
  • Airway fungal colonization in CF is linked to diminished lung function and exacerbations.
  • Antifungal triazoles are used for CF fungal infections, but their efficacy varies.

Purpose of the Study:

  • To review pharmacokinetic principles in CF patients.
  • To examine how CF affects azole antifungal pharmacokinetics.
  • To highlight the need for therapeutic drug monitoring of azoles in CF.

Main Methods:

  • Literature review of pharmacokinetic studies.
  • Analysis of CF-related physiological changes impacting drug metabolism.
  • Discussion of azole antifungal pharmacokinetics in the context of CF.

Main Results:

  • CF patients exhibit significant inter-subject variability in triazole serum concentrations.
  • Altered pharmacokinetics in CF can lead to sub-therapeutic or supra-therapeutic azole exposure.
  • Sub-therapeutic levels risk treatment failure and antifungal resistance.
  • Supra-therapeutic levels pose a risk of azole-related toxicity.

Conclusions:

  • Inconsistent azole levels in CF patients necessitate careful management.
  • Therapeutic drug monitoring of azoles is essential for optimizing treatment outcomes.
  • Monitoring helps mitigate risks of treatment failure, resistance, and toxicity in CF.
Keywords:
Cystic fibrosisInvasive fungal infectionPharmacokineticsTherapeutic drug monitoringTriazole antifungal antibiotics

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