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小型猪在药物发现与开发中的应用:小型猪选择的利弊及用作首选非啮齿类动物的策略

The Use of Minipig in Drug Discovery and Development: Pros and Cons of Minipig Selection and Strategies to Use as a Preferred Nonrodent Species.

作者信息

Heining Peter, Ruysschaert Tristan

机构信息

Preclinical Safety, Novartis Pharma AG, Basel, Switzerland

Preclinical Safety, Novartis Pharma AG, Basel, Switzerland.

出版信息

Toxicol Pathol. 2016 Apr;44(3):467-73. doi: 10.1177/0192623315610823. Epub 2015 Dec 16.

Abstract

The pig was introduced more than 20 years ago in drug development following attempts of finding a species that shares better homology with human than the dog, based on biophysiological parameters. However, miniaturization, standardized breeding, and health status control were required before the pig could find a broader than niche application in pharmaceutical industry. During the years of experience with minipigs in pharmaceutical research and the science evolving rapidly, the selection of a nonrodent animal species for preclinical safety testing became primarily driven by pharmacological (target expression homologous function), pharmacokinetic, and biophysiological considerations. This offered a broad field of application for the minipig, besides the well-established use in dermal projects in all areas of drug development but also in novel approaches including genetically modified animals. In this article, we look at recent approaches and requirements in the optimal selection of a nonrodent model in pharmaceutical development and critically ask how good a choice the minipig offers for the scientist, how did the testing environment evolve, and what are the key requirements for a broader use of the minipig compared to the other well-established nonrodent species like dog or monkey.

摘要

20多年前,基于生物生理参数,人们试图找到一种比狗与人类具有更好同源性的物种,猪因此被引入药物研发领域。然而,在猪能够在制药行业获得比特定小众应用更广泛的应用之前,需要进行小型化、标准化育种和健康状况控制。在对小型猪进行药物研究的多年经验以及科学迅速发展的过程中,选择一种非啮齿类动物进行临床前安全性测试主要受到药理学(靶点表达同源功能)、药代动力学和生物生理学因素的驱动。这为小型猪提供了广阔的应用领域,除了在药物研发所有领域的皮肤项目中已确立的用途外,还包括在转基因动物等新方法中的应用。在本文中,我们探讨了药物研发中选择非啮齿类模型的最新方法和要求,并批判性地思考小型猪对科学家来说是多好的一个选择、测试环境是如何演变的,以及与狗或猴子等其他成熟的非啮齿类物种相比,更广泛使用小型猪有哪些关键要求。

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