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聚焦安全药理学方法。

Methods in safety pharmacology in focus.

作者信息

Pugsley Michael K, Gallacher David J, Towart Rob, Authier Simon, Curtis Michael J

机构信息

Johnson & Johnson PR&D, Global Preclinical Toxicology/Pathology, Raritan, NJ 00869, USA.

出版信息

J Pharmacol Toxicol Methods. 2008 Sep-Oct;58(2):69-71. doi: 10.1016/j.vascn.2008.07.002. Epub 2008 Jul 22.

Abstract

This focused issue of the Journal of Pharmacological and Toxicological Methods is the fifth to highlight Methods in Safety Pharmacology and includes a number of articles from the 7th Annual Safety Pharmacology Society (SPS) meeting that was held in Edinburgh, Scotland, September 19-21, 2007. However, unlike issues of the past, in which content predominantly focused on cardiovascular issues (specifically QT interval prolongation, QT-HR correction methods and validation of non-clinical cardiovascular models) this issue is composed of a number of non-cardiovascular methods papers and review articles. Of particular interest to readers will be articles related to CNS studies, in particular neurobehavioral assessments in non-human primates and the effects of drugs in juvenile and adult rats (an article that may be relevant in light of recent EU/US pediatric legislation). While cardiovascular function may not dominate there are several useful methodological papers including an assessment of cardiovascular sensitivity of drugs in conscious and anesthetized non-human primates, and a mathematical model (fractal analysis) applied to canine heartbeat dynamics. A first for the journal is a paper by Vargas et al., (2008-this issue) in which members of the SPS formed a working group in order to assess and review safety pharmacology testing of biological therapeutic agents (specifically monoclonal antibodies, mAbs). The group provides recommendations that will likely shape regulatory strategy and discussions in the yet to be fully discussed area of biological safety testing. In the tradition of obtaining a perspective on industry safety pharmacology program practices Lindgren et al., (2008-this issue) provide the results of a recent SPS survey that examines ICH S7A and S7B trends, aspects of early 'frontloading' safety studies, abuse and dependence liability and Contract Research Organization (CRO) tests/assays used in safety assessment of core battery and supplementary organ systems. In keeping with the translation track aspect of the 2007 meeting is an overview of the Distinguished Service Award lecture to Dr. T. Hammond that discusses many aspects of safety pharmacology including its evolution, impact, value and translation of non-clinical findings to humans. Finally, perspectives are presented on the use of the zebrafish as an early safety pharmacology-screening assay.

摘要

《药理与毒理方法杂志》的这一专题是第五个聚焦于安全药理学方法的专题,其中收录了多篇来自2007年9月19日至21日在苏格兰爱丁堡举行的第七届年度安全药理学协会(SPS)会议的文章。然而,与过去的专题不同,过去的内容主要集中在心血管问题上(特别是QT间期延长、QT-HR校正方法以及非临床心血管模型的验证),而本期由多篇非心血管方法的论文和综述文章组成。读者特别感兴趣的将是与中枢神经系统研究相关的文章,尤其是非人灵长类动物的神经行为评估以及药物对幼年和成年大鼠的影响(鉴于最近欧盟/美国的儿科立法,这篇文章可能具有相关性)。虽然心血管功能并非主导内容,但仍有几篇有用的方法学论文,包括对清醒和麻醉的非人灵长类动物中药物心血管敏感性的评估,以及应用于犬类心跳动力学的数学模型(分形分析)。该杂志的首篇文章是瓦尔加斯等人(2008年,本期)撰写的,其中SPS成员成立了一个工作组,以评估和审查生物治疗药物(特别是单克隆抗体,mAbs)的安全药理学测试。该小组提出的建议可能会塑造生物安全测试这一尚未充分讨论领域的监管策略和讨论方向。按照获取行业安全药理学项目实践观点的传统,林德格伦等人(2008年,本期)提供了SPS最近一项调查的结果,该调查考察了ICH S7A和S7B的趋势、早期“前置”安全研究的各个方面、滥用和依赖倾向以及用于核心电池和补充器官系统安全评估的合同研究组织(CRO)测试/分析。与2007年会议的翻译主题相契合的是一篇对T. 哈蒙德博士杰出服务奖讲座的概述,该讲座讨论了安全药理学的许多方面,包括其演变、影响、价值以及非临床研究结果向人类的转化。最后,还介绍了将斑马鱼用作早期安全药理学筛选试验的观点。

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