良好的实验动物给药和采血规范指南

A Good Practice Guide to the Administration of Substances and Removal of Blood,Including Routes andVolumes良好的实验动物给药与采血(包括途径与体积)规范指南Karl-Heinz Diehl1, Robin Hull2, David Morton3, Rudolf Pfister4, Yvon Rabemampianina5,David Smith6,*, Jean-Marc Vidal7 and Cor van de V orstenbosch 81Aventis, PO Box 1140, D35001 Marburg, Germany德国马尔堡市35001区1140信箱安万特公司2N I B S C, Blanch Lane, South Miimms, Potters Bar, Hertfordshire EN6 3QG英国赫特福德郡EN6 3QG波特斯巴镇South Miimms布兰奇道英国国家生物制品检定所3The University of Birmingham, Medical School, Edgbaston, Birmingham B15 2TT英国伯明翰市B15 2TT艾吉马斯顿伯明翰大学医学院4Novartis Pharma AG, CH-4002 Basel, Switzerland瑞士巴塞尔CH-4002诺华制药公司5Centre de Recherche Pfizer, Etablissement d’Amboise, Z1 Poce´-sur-Cisse-BP 159 37401 Amboise Cedex, France法国Amboise Cedex Z1 Poce´-sur-Cisse-BP 159 37401 Etablissement d’Amboise 辉瑞研究中心6AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leics LE11 5RH英国莱斯特郡LE11 5RH拉夫堡市贝克韦尔路Charnwood阿斯利康研究中心7Aventis, 102 Route de Noisy, 95235 Romainville Ce´dex, France法国Romainville Ce´dex 95235 Noisy路102号安万特公司8N V Organon, PO Box 20, 5340 BH Oss, Netherlands荷兰BH Oss5340 20号信箱欧加农公司Key words: blood volumes; blood removal; administration substances; laboratory animals; refinement、关键词:血容量;采血;给药;实验动物;简化This article is the result of an initiative between the European Federation of Pharmaceutical Industries Associations (EFPIA) and the European Centre for the Validation of Alternative Methods (ECV AM)、Its objectives are to provide the researcher in the safety evaluation laboratory with an up-to-date, easyto-use set of data sheets to aid in the study design process whilst at the same time affording maximum welfare considerations to the experimental animals、该文章为欧盟制药工业协会(EFPIA)与欧洲替代动物实验方法验证中心(ECV AM)之间的初步结果。

其目的在于为安全性评价实验室的研究者提供最新的易于使用的数据库以帮助研究设计过程,同时最大可能地考虑到实验动物的福利。

Although this article is targeted at researchers in the European Pharmaceutical Industry, it is considered that the principles underpinning the data sets and refinement proposals are equally applicable to all those who use these techniques on animals in their research, whether in research institutes,universities or other sectors of industry、Theimplications of this article may lead to discussion with regulators, such as those responsible for pharmacopoeial testing、尽管该文章针对的就是欧洲制药工业界的研究者,但支撑该数据库的基本原理及改进建议同样适用于所有在她们的研究中使用这些动物实验技术的人,不论就是研究所、大学或其它行业中的研究者。

There are numerous publications dealing with the administration of test substances and the removal of blood samples, and many laboratories also have their own ‘in-house’ guidelines th at have been developed by custom and practice over many years、Within European Union Directive 86/609EEC1 we have an obligation to refine experiments to cause the minimum amount of stress、We hope that this article will provide background data useful to those responsible for protocol design and review、有关供试品给予与采血的出版物众多,且许多实验室在多年的经验与实践基础之上亦发展了它们自己的内部指南。

在欧盟化妆品标准86/609EEC中,我们有义务简化实验以最小化动物的紧张程度。

我们希望该文能够对那些负责方案设计与审核的研究者提供有用的背景数据。

This guide is based on peer-reviewed publications whenever possible, but where this is not possible we have used ‘in-house’ data and the experience of those on the working party (as well as helpful comments submitted by the industry) for a final opinion、The guide also addresses the continuing need to refine the techniques associated with the administration of substances and the withdrawal of blood, and suggests ways of doing so、Data-sharing between laboratories should be encouraged to avoid duplication of animal work, as well as sharing practical skills concerning animal welfare and sci entific problems caused by ‘overdosing’ in some way or another、The recommendations in this guide refer to the ‘normal’ animal, and special consideration is needed, for instance, during pregnancy and lactation、Interpretation of studies may be confounded when large volumes are administered or excessive sampling employed, particularly if anaesthetics are used、Copyright ã 2001 John Wiley & Sons, Ltd、该文章基于历年所有可能收集到的同行评议出版物,但我们未能够收集到的内部数据与那些工作组的经验(以及行业提交的有用的注释)除外。

该指南亦强调了持续性简化与给药与采血有关的技术的必要性,并且建议该如何去进行这方面的工作。

应该鼓励实验室间的数据共享以避免重复性动物研究,以及共享在某些方法或其它情况下的“药物过量”所引起的与动物福利有关的实际技术与科学问题。

有必要对该指南中涉及到的“正常动物”要求进行特殊考虑,如妊娠与哺乳期间的动物。

当给药体积较大或过度采样时对研究结果的诠释可能会令人感到困惑,特别就是使用麻醉动物时。

GOOD PRACTICE GUIDE FOR ADMINISTRATION OF SUBSTANCES良好的给药规范指南Introduction引言Dosing of experimental animals is necessary for a variety of scientific investigations and to meet regulatory demands、The pharmaceutical industry, in particular,has investigated the levels of dosing compatible with animal welfare and valid science、2 In the preclinical stage of the safety evaluation of new drugs it is normal practice to usemultiples of the ‘effective dose’in order to attempt to establish the necessary safety margins、Where chemicals are of low toxicity or are only poorly soluble in acceptable formulations, a large volume may be required to be given to individual animals to satisfy both scientific and regulatory requirements、The intended clinical use may also have an impact on the acceptability of larger than usual dose volumes, e、g、imaging agents or plasma expanders for intravenous application、各种科学研究都需要对实验动物给药以符合药品注册要求。