注射用美洛西林钠舒巴坦钠的特殊安全性试验延展和再评价

目的 注射用美洛西林钠舒巴坦钠的特殊安全性试验的延展和再评价。方法 将注射用美洛西林钠舒巴坦钠用生理盐水配制成不同浓度,观察体外溶血试验中,是否有溶血和血细胞凝集作用,家兔耳缘静脉注射后血管刺激性,以及豚鼠的被动皮肤过敏反应。并根据《中国药典》2010年版二部附录进行注射用无菌粉末的pH值、不溶性微粒和渗透压检查试验。结果 注射用美洛西林钠舒巴坦钠在临床用药浓度下符合规定,高于此浓度时有体外凝血、溶血现象出现,且家兔耳缘静脉出现血管炎症和血栓形成。而其渗透压和不溶性微粒仅在10倍临床用药浓度时超标。因此对血细胞和血管上皮细胞的损伤为药物本身所致。在豚鼠能承受的最大剂量下无被动皮肤过敏反应。结论 注射用美洛西林钠舒巴坦钠在规定的用药浓度下有关安全性检测结果符合新药申报要求。临床用药时应严格遵循规定,避免对血细胞和上皮细胞的损伤。特殊安全性试验的延展很有必要。

Expanding and Re-assessment of Special Safety of Mezlocillin Sodium and Sulbactam Sodium for Injection

Objective To expand the experimental data and re-evaluate the special safety of Mezlocillin Sodium and Sulbactam Sodium for Injection. Methods The inspection of hemolysis and cohesion through in vitro hemolysis test, the vascular irritation of rabbit auricular vein, and passive cutaneous anaphylaxis were carried out with different concentrations of Mezlocillin Sodium and Sulbactam sodium for Injection in saline solution, which pH value, particulate matter and osmotic pressure molar concentration (OPMC) were determined according to the methods in the appendix of Chinese Pharmacopoeia 2010 Part II, as well. Results Mezlocillin Sodium and Sulbactam sodium for Injection had no vascular irritation and injury effect on rabbit vascular endothelial cell, and no evidences of hemolyzation and aggregation on rabbit erythrocyte at required clinical concentration, whereas the vasculitis and thrombosis were observed when this concentration increased. Since the particulate matter and OPMC exceeded the standard only when more than 10 times of its clinical concentration, the damage must be caused by the drug itself. No allergic reaction on guinea pig skin was observed at the maximum tolerated dose. Conclusion The results of special safety tests fit the new drugs application requirement at clinical concentration. This concentration should be strictly followed in clinical use to prevent from the damage of erythrocyte and endothelial cell by the drug itself. It is necessary to expand the special safety tests.