苯环喹溴铵吸入气雾剂人体耐受性研究  

Human tolerance study of bencycloquidium bromide pressurized-metered dose inhaler

作　　者：罗柱[1] 胡超[1] 苗佳[1] 王颖[1] 舒世清[1] 朱晓红[1] 张辉明[1] 门宇春[1] 梁茂植[1] LUO Zhu;HU Chao;MIAO Jia;WANG Ying;SHU Shi-qing;ZHU Xiao 一 hong;ZHANG Hui-ming;MEN Yu -chun;LIANG Mao-zhi(Institute of Drug Clinical Trial/ GCP Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China)

机构地区：[1]四川大学华西医院国家药物临床试验机构/GCP中心

出　　处：《中国临床药理学杂志》2019年第13期1333-1336,共4页The Chinese Journal of Clinical Pharmacology

基　　金：四川省科技厅重大支撑基金资助项目项目(2018SZ0001)

摘　　要：目的观察苯环喹溴铵吸入气雾剂在中国健康受试者的单次和连续用药的耐受性,评估其安全剂量范围。方法单次给药阶段为7个剂量组,每组8例,男女各半,给药剂量分别为125,250,500,750,1125,1500,2000μg。连续给药阶段为2个剂量组,每组8例,男女各半,给药剂量为1500,2000μg·d^-1,分4次给药,连续给药14 d。单次和连续给药每剂量组设安慰剂对照2例,男女各1例。安全性评价指标包括用药后临床症状、生命体征、体格检查、实验室检查、胸片、腹部彩超、心电图等辅助检查。结果共纳入72例健康受试者,均按方案完成研究。单次给药阶段56例受试者中有5例发生了5例次药物不良事件,各剂量组不良事件发生率差异无统计学意义,无重要不良事件和严重不良事件。单次给药在125~2000μg均可耐受,最大耐受剂量为2000μg。连续给药阶段16例受试者中有7例发生了9例次不良事件,各剂量组不良事件发生率差异无统计学意义,无重要不良事件和严重不良事件。上述不良事件程度均为轻度,未采取措施即恢复正常。结论单次和连续给药耐受性试验均提示苯环喹溴铵吸入气雾剂具有良好的安全性,单次给药最大耐受剂量为每次2000μg;连续给药1500,2000μg·d^-1,分4次给药,连续给药14 d,安全性好。Objective To study the safety and tolerance of bencycloquidium bromide pressurized - metered dose inhaler on single and multiple dosing in healthy Chinese volunteers and evaluate the dosing range in human body. Methods In single dosing period,eligible subjects were enrolled and assigned into 7 groups to receive a single dose of 125,250, 500,750,1125,1500 and 2000 μg,respectively. In multiple dosing period,eligible subjects were enrolled and assigned into 2 groups to receive multiple dosing of 1500 and 2000 μg per day ( qid),respectively for 14 d. The case number in each group was 8 and male∶ female was 1∶ 1. Placebo control was used in each group with 2 cases . Tolerability was evaluated by monitoring clinical symptoms,physical examinations, laboratory tests,X - rays,abdominal ultra - sonic scan and electrocardiogram,etc. Results Totally 72 healthy subjects were enrolled and all of them completed the study. In single dosing period,5 of the 56 subjects reported 5 cases of adverse events,no important or severe adverse event was observed. Single dosing of 125 - 2000 μg was well tolerated and the maximum single tolerance dose was 2000 μg. In multiple dosing period,7 of the 16 subjects reported 9 cases of adverse events,no important or severe adverse event was observed. All the adverse events were mild and recovered without any medical treatment. Conclusion Single and multiple dosing of bencycloquidium bromide pressurized - metered dose inhaler were well tolerated by healthy Chinese subjects. The maxi-mum single tolerance dose was 2000 μg;multiple dosing of 1500 and 2000 μg per day ( qid) for 14 d were well tolerated.

关 键 词：苯环喹溴铵 吸入气雾剂 Ⅰ期临床试验 人体耐受性 

分 类 号：R97[医药卫生—药品]