Extrapolating Antifungal Animal Data to Humans - Is it reliable?

Area of Science:

• Pharmacology
• Infectious Diseases
• Translational Medicine

Background:

• Animal models are essential tools in preclinical research for evaluating antifungal agents.
• Invasive fungal infections pose significant global health challenges, necessitating robust drug development pipelines.

Purpose of the Study:

• To review the utility of animal models in antifungal research.
• To assess the reliability of extrapolating findings from animal studies to human clinical outcomes.

Main Methods:

• Literature review of animal models used in antifungal research.
• Comparative analysis of animal study results with human clinical data.

Main Results:

• Animal models have successfully guided the identification of therapeutic targets (AUC/MIC) and effective drug combinations for fungal infections like aspergillosis.
• Successful translation of animal model findings to human outcomes was observed for drugs such as isavuconazole and posaconazole.
• Challenges exist in replicating human pharmacokinetics in animal models, impacting drug efficacy, as seen with itraconazole formulations.
• Discrepancies in outcomes were noted, such as survival benefits in animal models for mucormycosis with iron chelators and amphotericin, which were not replicated in humans.

Conclusions:

• Animal models are invaluable for optimizing antifungal agents and studying rare diseases like invasive fungal infections.
• Despite their benefits, limitations in animal models necessitate critical evaluation when extrapolating data to human applications.
• Ongoing research is needed to refine animal models for improved prediction of human responses to antifungal therapies.