Stevens Victoria M, Mueller Scott W, Reynolds Paul M, MacLaren Robert, Kiser Tyree H
Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, 12850 East Montview Boulevard, Mail Stop C238, Aurora, CO 80045, USA.
Curr Fungal Infect Rep. 2020 Mar;14(1):50-62. doi: 10.1007/s12281-020-00370-x. Epub 2020 Jan 16.
This article aimed to review animal models of antifungals and identifies human literature to assess if the extrapolation of results is reliable.
Animal studies have helped identify AUC/MIC 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.
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.
本文旨在回顾抗真菌药物的动物模型，并查找相关人类文献以评估结果外推是否可靠。
动物研究有助于确定新药和制剂（如艾沙康唑和缓释泊沙康唑）的AUC/MIC靶点，这些靶点已转化为人类的成功治疗结果。模型在确定治疗曲霉病的可能联合疗法（如伏立康唑和棘白菌素）方面也具有影响力。然而，在复制人类药代动力学方面，动物模型面临挑战，最新的伊曲康唑制剂就是例证。此外，动物模型显示使用铁螯合剂和两性霉素治疗毛霉病有生存获益，但在人类中并未得到证实。
动物模型一直是抗真菌药物研发和优化的主要手段。它们能够研究罕见疾病，如侵袭性真菌感染，否则研究此类疾病需要数年时间和大量资源。尽管动物模型有诸多益处，但也存在缺点。这就是为何从动物模型向人类外推数据的可靠性常受到审视的原因。
