Extrapolating Antifungal Animal Data to Humans - Is it reliable?

IF 2.3 Q3 INFECTIOUS DISEASES Current Fungal Infection Reports Pub Date : 2020-03-01 Epub Date: 2020-01-16 DOI:10.1007/s12281-020-00370-x

Victoria M Stevens, Scott W Mueller, Paul M Reynolds, Robert MacLaren, Tyree H Kiser

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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 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.

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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将抗真菌动物数据推断给人类--可靠吗？

综述目的：本文旨在回顾抗真菌药物的动物模型，并对人类文献进行鉴定，以评估外推结果是否可靠：动物研究有助于确定新药和新制剂（如异武康唑和缓释泊沙康唑）的AUC/MIC目标，从而在人体中取得成功。在确定治疗曲霉菌病的可能联合疗法（如伏立康唑和棘菌素）方面，动物模型也发挥了重要作用。然而，动物模型在复制人体药代动力学方面面临挑战，最新的伊曲康唑制剂就是一个例子。此外，动物模型在使用铁螯合剂和两性霉素治疗粘孢子菌病时显示出了生存优势，而这在人类身上并未得到证实。动物模型能够研究侵袭性真菌感染等不常见疾病，否则将需要数年时间和大量资源才能完成。虽然动物模型有很多优点，但也有不足之处。因此，从动物模型向人类推断数据的可靠性经常受到审查。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Fungal Infection Reports INFECTIOUS DISEASES-

CiteScore

3.10

自引率

7.10%

发文量

期刊介绍： This journal intends to provide clear, insightful, balanced contributions that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of fungal infections. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as advances in diagnosis, current and emerging management approaches, and genomics and pathogenesis. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. Commentaries from well-known figures in the field are also provided, and an international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research.