多次静脉滴注磷酸左奥硝唑酯二钠的Ⅰ期临床耐受性试验  

Phase Ⅰ Clinical Trial on Safety and Tolerability of Levornidazole Disodium Phosphate for Injection in Chinese Healthy Volunteers

作　　者：曹江[1] 陈迁[2] 梅和坤[1] 白楠[1] 江学维[1] 王瑾[1] 王睿[1] 

机构地区：[1]中国人民解放军总医院药物临床研究中心,北京100853 [2]中国人民解放军总医医学转化中心,北京100853

出　　处：《中国药物警戒》2016年第5期260-262,274,共4页Chinese Journal of Pharmacovigilance

基　　金：十二五国家重大科技专项(2012ZX09303004-002)

摘　　要：目的观察1.1类新药注射用磷酸左奥硝唑酯二钠在健康人体多次给药的耐受性。方法将有24名受试者参加本试验(男女各半),分为两个剂量组,分别滴注剂量为1 000 mg/次,每天2次;2 000 mg/次,每天1次连续给药7天,进行多次静脉滴注注射用磷酸左奥硝唑酯二钠的耐受性试验。结果在多次耐受试验中,受试者用药前后生命体征、心电图没有临床意义的改变。有12例受试者发生19例不良事件,其中丙氨酸氨基转移酶、天门冬氨酸氨基转移酶升高、血乳酸脱氢酶升高、输注部位疼痛与研究药物有一定的关联性,但均较轻微,持续时间短,未经干预,均自行缓解和消失,无严重不良事件和导致脱落的不良事件发生。结论多次给药1 000 mg/次,每天2次;2 000 mg/次,每天1次,连续给药7天耐受性良好,主要不良反应表现为:ALT、AST轻度升高,也符合奥硝唑主要经肝脏清除的规律,其中2 000 mg/次,每天1次给药组安全性和耐受性优于1 000 mg/次,每天2次组。Objective To assess the safety and tolerability of levornidazole disodium phosphate for injection in Chinese healthy volunteers. Methods 24 healthy subjects were enrolled in the multi-dose trial（male：female=1：1）. Subjects were equally divided into two groups, received intravenous infusion of 1 000 mg twice daily and 2 000 mg once daily for consecutive 7 days. The safety and tolerability were evaluated based on clinical symptoms, vital signs, physical examinations, ECG, laboratory tests and adverse events. Results Levornidazole disodium phosphate had no clinically signifi cant effects on vital signs and ECG in total of 24 subjects who completed the tolerance test. 19 adverse events were observed in 12 subjects, including ALT elevation, AST elevation, LDH elevation and pain at the injection site, which were somewhat related to the study drug judged by investigator. But they were slight and temporary and completely relieved without any intervention. There was no serious adverse event or any adverse event leading to drop-out. Conclusion Levornidazole disodium phosphate for injection is well-tolerated in Chinese healthy subjects after administration of multi-doses（1 000 mg twice daily and 2 000 mg once daily）. The main adverse reactions were ALT and AST mild increase, which were also consistent with previous reports that hepatic metabolism is the main elimination for ornidazole. In the multi-dose trial, safty and tderability of 2 000 mg once daily is bettert than that of the other.

关 键 词：注射用磷酸左奥硝唑酯二钠 多次静脉滴注 耐受性试验 

分 类 号：R969.4[医药卫生—药理学]