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将抗真菌动物实验数据外推至人类——这可靠吗?

Extrapolating Antifungal Animal Data to Humans - Is it reliable?

作者信息

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

机构信息

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.

出版信息

Curr Fungal Infect Rep. 2020 Mar;14(1):50-62. doi: 10.1007/s12281-020-00370-x. Epub 2020 Jan 16.

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.

摘要

综述目的

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。

最新发现

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。

总结

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。

相似文献

1
Extrapolating Antifungal Animal Data to Humans - Is it reliable?将抗真菌动物实验数据外推至人类——这可靠吗?
Curr Fungal Infect Rep. 2020 Mar;14(1):50-62. doi: 10.1007/s12281-020-00370-x. Epub 2020 Jan 16.
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Pros and Cons of Extrapolating Animal Data on Antifungal Pharmacodynamics to Humans.将动物抗真菌药效学数据外推至人类的利弊
Curr Fungal Infect Rep. 2011 Jun;5(2):59-66. doi: 10.1007/s12281-011-0051-0. Epub 2011 Mar 26.

本文引用的文献

1
Pros and Cons of Extrapolating Animal Data on Antifungal Pharmacodynamics to Humans.将动物抗真菌药效学数据外推至人类的利弊
Curr Fungal Infect Rep. 2011 Jun;5(2):59-66. doi: 10.1007/s12281-011-0051-0. Epub 2011 Mar 26.
5
Extended Dosing Regimens for Fungal Prophylaxis.延长疗程的真菌预防用药方案。
Clin Microbiol Rev. 2019 May 15;32(3). doi: 10.1128/CMR.00010-19. Print 2019 Jun 19.

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