药物安全性评价中豚鼠全身过敏试验方法的研究

Research on the Methods of Active Systemic Anaphylaxis on Guinea Pig in Drug Safety Evaluation

目的在新药临床前安全性评价中对药物致敏性的研究日益受到重视。本实验基于我国新药评价指导原则,分析探讨SFDA颁布的指导原则中豚鼠全身过敏实验方案中可能影响实验结果的问题和因素。方法在GLP条件下,以体重为300～400克的豚鼠为实验对象,以牛血清白蛋白、生理盐水等受试物为对照,研究不同致敏剂量、激发剂量、激发时间、激发途径和激发次数等条件下,豚鼠全身过敏的发生情况。结果在一定剂量范围内,豚鼠全身过敏反应的发生率与致敏剂量、激发剂量和激发途径无关,但症状发生的严重程度与致敏剂量、激发剂量和激发途径有关。结论新药过敏性评价研究应参照指导原则,注意试验的剂量设计和给药途径。

Objective To analyze some potential factors which might affect the active systemic anaphylaxis（ASA） test on guinea pig.Methods In GLP conditions,guinea pigs from 300 to 400 grams were used as experimental subjects.By using the materials including bovine serum albumin and saline which are recommended for the control subjects by the guidelines,some experimental design factors such as sensitizing dose,challenge dose,challenge interval and challenge injection route,and the frequency of challenge were studied during the systemic anaphylaxis in guinea pigs.Results In a certain dose range,the incidence of allergic reactions in guinea pigs was not related with systemic sensitizing dose,challenge dose and challenge injection approach,but the severity of anaphylaxis symptoms has an obvious relationship with sensitizing dose,challenge dose and challenge injection route.Conclusion Study on the drug-induced anaphylaxis should refer to the guidelines and pay more attention to experimental design dose and the route of administration.