药物过敏和类过敏临床前评价要求概述.docVIP

药物过敏和类过敏临床前评价要求概述 　　[摘要]药物过敏和类过敏反应是主要的不可预测药物不良反应。过敏反应一般由药物、药物代谢产物或药物添加剂的免疫原性引起;类过敏反应可能是由药物刺激或激活炎症介质的释放而引起的。药物过敏和类过敏反应的临床前评价属于免疫毒性评价的范畴。由于不同类型过敏和类过敏反应的发生机制不同，目前没有任何一种体内或体外方法可以预测所有类型的反应。近年来FDA，SFDA，OECD，ICH，WHO等颁布了一系列针对药物免疫毒性临床前评价的指导原则，但目前关于新药临床前过敏和类过敏反应评价的要求和方法尚未完全统一。该文主要就药物过敏和类过敏的临床前评价要求进行综述。 　　[关键词]药物致敏性评价;药物过敏;药物类过敏;免疫毒性指导原则 　　Review on requirements of drug allergy or pseudoallergic 　　reactions in pre-clinical evaluation 　　HAN Jia-yin， YI Yan， LIANG Ai-hua*， ZHANG Yu-shi， LI Chun-ying， ZHAO Yong， WANG Lian-mei， LU Yu-ting， LI Gui-qin 　　（Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine， Institute of Chinese 　　Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700， China） 　　[Abstract]Drug allergy and pseudoallergic reactions are main adverse drug reactions. Allergy is mainly induced by the immunogenicity of drug， drug metabolic products or drug additive. Pseudoallergic reactions may result from the irritation or activation of inflammatory material release. Pre-clinical evaluation of drug allergy and pseudoallergic reactions is included in immunotoxicity evaluation. Now there is no in vivo or in vitro method that could predict all kinds of allergy or pseudoallergic reactions due to the different mechanisms. In the past few years， FDA， SFDA OECD， ICH and WHO have published several guidelines on per-clinical immunotoxicity evaluation， however， no agreement has been reached on allergy and pseudoallergic reactions evaluation. This article reviews the requirements of allergy and pseudoallergic reactions in pre-clinical evaluation. 　　[Key words]drug sensitization evaluation; drug allergy; drug pseudoallergic reactions; immunotoxicity guideline 　　doi：10.4268/cjcm 　　药物过敏反应是药物免疫毒性中免疫增强的一种，一般由药物、药物代谢产物或药物添加剂的免疫原性引起，其临床前评价属于免疫毒性评价的范畴。一般情况下，大分子生物药物可能作为全抗原刺激机体产生过敏反应，而小分子化学药物则不具备明显的抗原性，只能作为半抗原，需要进入体内后与大分子结合成为全抗原而导致反应。目前，过敏反应根据所产生的抗体类型、临床症状及组织损伤机理、抗原与相应抗体或致敏淋巴细胞作用的方式、补体是否参加等分为4型即：Ⅰ型（速发型）、Ⅱ型（细胞毒型）、Ⅲ型（免疫复合