非临床安全性评价研究中注射用阿奇霉素豚鼠过敏试验研究  

Allergic test of azithromycin for injection in guinea pigs in non-clinical safety evaluation

作　　者：刘春[1] 王巨才[1] 黄裕昌 叶小青[1] 赵映淑[1] 詹媚媚 王晨[2] LIU Chun;WANG Jucai;HUANG Yuchang;YE Xiaoqing;ZHAO Yingshu;ZHAN Meimei;WANG Chen(Hainan Institute for Drug Control,Haikou Hainan 570216,China;National Institutes for Food and Drug Control,Beijing,102629,China)

机构地区：[1]海南省药品检验所,海南海口570216 [2]中国食品药品检定研究院,北京102629

出　　处：《中国药物警戒》2022年第11期1161-1164,1169,共5页Chinese Journal of Pharmacovigilance

基　　金：国家重点研发计划(SQ2022YFC3400054)。

摘　　要：目的 通过对注射用阿奇霉素进行豚鼠过敏试验研究,评价非临床安全性评价研究中过敏试验方法。方法 主动全身过敏试验中,试验I为将豚鼠随机分为阴性对照组、阳性对照组、低剂量组(2.5 mg·kg^(-1))和高剂量组(10 mg·kg^(-1)),隔日致敏1次,共致敏3次,于末次致敏后第14天和第21天激发观察豚鼠是否出现过敏反应症状。试验II除高剂量组剂量调整为5 mg·kg^(-1)外,其余同试验I;被动皮肤过敏试验中,2次试验剂量同全身主动过敏试验,在末次致敏后第11天采血制备抗血清,皮内注射各对应组的抗血清被动致敏。24 h后静脉注射激发,测量皮肤内层的蓝斑直径。结果 全身主动过敏试验中,试验I在第14天激发后,注射用阿奇霉素给药组均未见过敏反应症状,第21天激发后,高剂量组3只豚鼠出现搔鼻、哮鸣等过敏反应症状。试验II结果为在第14天和第21天激发后均未见过敏反应症状。被动皮肤过敏试验两次试验阳性对照组结果均为阳性,致敏率100%,注射用阿奇霉素组对豚鼠均无被动皮肤过敏反应。结论 过敏反应的发生与剂量和致敏时间有一定关系,但方法存在一定局限性,在符合指导原则的情况下,临床也可能引起过敏反应,在新药非临床安全性评价研究中需关注。Objective To evaluate the allergic test methods in non-clinical safety evaluation by investigating allergic reaction of guinea pigs induced by azithromycin for injection. Methods The active systemic anaphylaxis(ASA):Guinea pigs were randomly divided into negative control group, positive control group, low-dose group(2.5 mg·kg)and high-dose group(10 mg·kg^(-1)) in experiment I.The intraperitoneal injections of azithromycin for injection were administrated to guinea pigs once every other day for three times. On the 14th and 21st days after the last sensitization, the symptom of allergic reaction was observed by intravenous administration of azithromycin for injection. The other methods were same as the experiment I, except the dose of high-dose group was set at 5 mg·kg^(-1)in experiment II.The doses of passive cutaneous anaphylaxis(PCA) were as same as the ASA. On the 11th day after the last sensitization, antiserums were prepared. Guinea pigs of each group were injected intradermally by diluted antiserum. The blue spot diameter in skin was measured after intravenous administration of the same doses after 24 hours. Results No systemic allergic reaction was observed on guinea pigs administrated of azithromycin on the 14th day after the last sensitization in experiment I of ASA. The symptom of nose-scratching or wheezing sound was observed in high-dose group after intravenous administration of azithromycin on the 21st day in experiment I of ASA. No systemic hypersensitive reaction was observed both on the 14th and 21st days in experiment II of ASA. The positive reaction was observed in positive control group, while no allergic reaction was observed in the azithromycin administration group of PCA. Conclusion The occurrence of allergic reactions may be related with the dose and the sensitization time. The method has its own limitations. More focus may be given to the allergic test in non-clinical safety evaluation, because even if it meets the guiding principles, allergic reactions may also be caused.

关 键 词：阿奇霉素 注射剂 主动全身过敏试验 被动皮肤过敏试验 过敏反应 方法评价 

分 类 号：R965[医药卫生—药理学]