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Dose tolerability of chronically inhaled voriconazole solution in rodents

Justin A Tolman1, Nicole A Nelson, Stephanie Bosselmann

  • 1The University of Texas at Austin College of Pharmacy, Austin, TX, United States.

International Journal of Pharmaceutics
|June 16, 2009
PubMed

Insights

Inhaled voriconazole demonstrates good tolerability and achieves therapeutic lung concentrations in a rat model. This targeted drug delivery offers a promising approach for treating invasive pulmonary aspergillosis (IPA).

Area of Science:

  • Pharmacology
  • Pulmonology
  • Mycology

Background:

  • Invasive pulmonary aspergillosis (IPA) presents a significant mortality risk in immunocompromised individuals.
  • Current treatments for IPA have limitations, necessitating novel drug delivery strategies.
  • Previous research indicated that targeted voriconazole delivery enhances drug concentrations and survival in a murine IPA model.

Purpose of the Study:

  • To evaluate the tolerability and pharmacokinetic profile of inhaled voriconazole in a rat model.
  • To assess the safety and efficacy of aerosolized voriconazole for potential IPA treatment.

Main Methods:

  • Rats received nebulized normal saline (control), low-dose, or high-dose aerosolized voriconazole.
  • Lung tissue and plasma voriconazole concentrations were measured after 3 and 21 days of twice-daily dosing.
  • Laboratory values and histopathology were analyzed to assess safety and tolerability.

Main Results:

  • Inhaled voriconazole achieved measurable concentrations in rat lung tissue and plasma.
  • Low-level drug accumulation was observed over 21 days with twice-daily dosing.
  • Statistically significant but clinically irrelevant laboratory abnormalities and increased alveolar macrophages were noted.
  • Inhaled voriconazole was well-tolerated, with no observed airway inflammation or edema.

Conclusions:

  • Inhaled voriconazole is well-tolerated in rats, suggesting a potentially safe delivery route.
  • The study demonstrates the feasibility of achieving therapeutic voriconazole concentrations in the lungs via inhalation.
  • Targeted inhaled voriconazole warrants further investigation as a treatment strategy for invasive pulmonary aspergillosis.

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