阿奇霉素缓释阴道栓局部刺激性和急性毒性试验

Experimental study on the acute toxicity and mucosal irritation of azithromycin sustained-release vaginal suppository

目的:研究阿奇霉素缓释阴道栓的局部刺激性和急性毒性,旨在为该制剂用于临床提供理论依据。方法:根据临床推荐用药方案计算新西兰兔的阴道给药量和疗程。末次给药后24h处死动物,解剖取出阴道组织进行肉眼观察和病理组织检查;新西兰兔一日内阴道给予大剂量阿奇霉素缓释阴道栓(140mg·kg-1.d-1),观察给药后2周内动物的情况。结果:新西兰兔连续阴道给予阿奇霉素缓释阴道栓7d,食欲、精神和活动正常;病理组织检查发现阿奇霉素缓释阴道栓组和基质空白栓组均未出现黏膜层细胞坏死脱落及固有层多量炎性细胞浸润现象。大剂量阿奇霉素缓释阴道栓给药后2周内无动物死亡。结论:阿奇霉素缓释阴道栓阴道局部用药无明显毒性及刺激性,其临床使用安全可靠。

OBJECTIVE Study on the acute toxicity, potential irritation on vaginal mucous membrane of azithromycin sustained-release vaginal suppository was performed to provide theoretical basis for this preparation in clinics. METHODS The dose and course for New Zealand rabbit were based on medication schedule of clinical recommendation. The rabbits should be sacrificed in 24 h after the last madication and vaginal tissues were dissected out for visual and histopathology observations. The rabbits were delivered the high doses of suppository （140mg·kg^-1·d^-1） once daily for two weeks. RESULTS The animals showed normal apepitites, mental state and activities after recieving the suppository for 7 consecutive days. Histopathological examinations revealed no necrosis of mucosa cells and no large number of inflammatory cell infiltration in lamina propria in both azithromycin group and vehicle group, as well as no animal death after the administration of high-dose suppository for two weeks. CONCLUSION Azithromycin sustained-release vaginal suppository did not induce acute toxicity and severe mucosal irritation , and it could be used safely in clinical practice.