注射用银黄Ⅰ期临床耐受性试验  

Phase Ⅰ Clinical Trial on Tolerability of Yinhuang Injection

作　　者：冯萍[1] 勾忠平[1] 邹林玲[1] 郑莉[1] 徐楠[1] 王颖[1] 罗柱[1] 沈奇[1] 吴松泽[2] 

机构地区：[1]四川大学华西医院国家药物临床试验机构,成都610041 [2]四川大学华西医院普内科,成都610041

出　　处：《中国循证医学杂志》2012年第3期278-282,共5页Chinese Journal of Evidence-based Medicine

摘　　要：目的观察注射用银黄在健康志愿者中的安全性和耐受性。方法单次给药剂量组32例健康志愿者分为7个剂量组,各组例数分别为2、4、6、6、6、4、4例,分别给予注射用银黄40、120、240、320、400、480和560 mg。多次给药剂量组12例健康志愿者分为2个剂量组,每组6例,分别给予注射用银黄240 mg及400 mg,每天1次,连续给药7天。观察受试者用药后不同时段的体温、心率、血压、临床症状和体征、以及不良事件发生情况,并在用药前后进行实验室检查和心电图检查。采用SAS 9.1软件进行统计分析,定量指标采用t检验及方差分析,定性指标采用卡方检验或确切概率法。结果共44例健康志愿者完成了耐受性试验。用药后生命体征、实验室及心电图检查均未发现有临床意义的异常。单次、多次试验均未发生严重不良事件及过敏反应。44例受试者中发生2例轻度不良事件,其中1例受试者(单次给药480 mg组)发生头晕,与试验药物可能有关。结论注射用银黄在40～560 mg范围内用药的安全性和耐受性良好,单次给药的最大耐受剂量为560 mg。多次给药240 mg及400 mg每天1次,连续给药7天的耐受性较好。推荐Ⅱ期临床试验的给药方案为240～400 mg/d。To assess the tolerability and safety of Yinhuang injection in Chinese healthy volunteers. Methods Thirty-two healthy subjects were enrolled in the single-dose study. Each subject was administered one of the seven doses of 40, 120, 240, 320, 400, 480, and 560 rag, respectively, by intravenous injection. The sample sizes were 2, 4, 6, 6, 6, 4 and 4, respectively, for each dose group. Twelve healthy subjects were enrolled in the multi-dose study. The subjects in the lower dose group were administered 240 mg and the subjects in the higher dose group were administered 400 nag Yin- huang by intravenous injection once a day for consecutive 7 days. The sample sizes for both groups were 6. The safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiogram （ECG）, laboratory tests and adverse events. All analyses were performed by using the software package SAS version 9.1. T-test and analysis of variance were used for continuous variables. Chi-square test and Fisher＇s exact test were used for categorical variables. Results A total of 44 healthy volunteers completed the tolerance test. No serious adverse event and clinically significant changes in vital signs, ECG and laboratory tests were found in both single-dose groups and multi-dose groups. Among two mild ad- verse events, dizziness occurred in one subject in 480 mg dose group in the single-dose trial, which was probably related to the experimental drug. Conclusion Yinhuang injection is safe and well-tolerated in Chinese healthy subjects after ad- ministration of single-doses （40-560 mg） and multi-doses （240-400 mg once a day for consecutive 7 days）. The maximum- tolerated dose of Yinhuang injection is at 560 mg in the single-dose trial. The dose regimen of 240-400 mg a day is recom- mended for phase II study.

关 键 词：注射用银黄 单次给药 多次给药 Ⅰ期临床试验 耐受性 

分 类 号：R285[医药卫生—中药学]