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Extrapolating Antifungal Animal Data to Humans—Is It Reliable?

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Abstract

Purpose of Review

This article aimed to review animal models of antifungals and identifies human literature to assess if the extrapolation of results is reliable.

Recent Findings

Animal studies have helped identify area under the concentration curve to minimum inhibitory concentration ratio targets for new drugs and formulations such as isavuconazole and delayed-release posaconazole that have translated to successful outcomes in humans. Models have also been influential in the identification of possible combination therapies for the treatment of aspergillosis, such as voriconazole and echinocandins. However, challenges are endured with animal models when it comes to replicating the pharmacokinetics of humans which has been exemplified with the newest itraconazole formulation. Additionally, animal models have displayed a survival benefit with the use of iron chelators and amphotericin for mucormycosis which was not demonstrated in humans.

Summary

Animal models have been a staple in the development and optimization of antifungal agents. They afford the ability to investigate uncommon diseases, such as invasive fungal infections, that would otherwise take years and many resources to complete. Although there are many benefits of animal models, there are also shortcomings. This is why the reliability of extrapolating data from animal models to humans is often scrutinized.

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Correspondence to Tyree H. Kiser.

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Conflict of Interest

Victoria Stevens reports grants from NCATS/NIH CTSA Grant UL1TR001082 during the conduct of the study. Scott Mueller reports grants from CSL Behring Investigator-Initiated Study and grants from Merck Investigator-Initiated Studies Program. All funding has been received by the institution that employs Scott Mueller and is outside the submitted work (unrelated to antifungal therapeutics). Tyree Kiser reports grants from NCATS/NIH CTSA Grant UL1TR001082 during the conduct of the study; grants from Astellas, grants from Allergan, and grants from Pfizer outside the submitted work. Paul Reynolds and Robert MacLaren declare no conflicts of interest relevant to this manuscript.

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This article is part of the Topical Collection on Pharmacology and Pharmacodynamics of Antifungal Agents

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Stevens, V.M., Mueller, S.W., Reynolds, P.M. et al. Extrapolating Antifungal Animal Data to Humans—Is It Reliable?. Curr Fungal Infect Rep (2020). https://doi.org/10.1007/s12281-020-00370-x

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Keywords

  • Triazole
  • Echinocandin
  • Amphotericin B
  • Animal model
  • Pharmacodynamics
  • Murine
  • Rabbit
  • Invasive fungal infection
  • Amphotericin B
  • Fluconazole
  • Voriconazole
  • Posaconazole
  • Itraconazole
  • Isavuconazole
  • Caspofungin
  • Micafungin
  • Anidulafungin
  • Rezafungin