尿NAG酶在中药首次健康人体试验肾脏安全性评价中的应用  

Application of urinary NAG in renal safety evaluation of TCM in an initial human trial

作　　者：李睿[1] 唐旭东[1] 高洪阳 赵迎盼[1] 侯金茹[1] 王淑阁[1] 赵阳[1] 高蕊[1] 

机构地区：[1]中国中医科学院西苑医院,北京100091

出　　处：《中国新药杂志》2015年第13期1462-1466,共5页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2012ZX09303-010-002);国家中医药管理局中医药行业科研专项(201207001-02)

摘　　要：目的:探讨尿NAG酶在首次健康人体试验肾脏安全性评价中的合理应用及评价思路。方法:采用随机、开放、空白对照、单/多剂量、口服给药的试验设计,40例健康受试者随机接受7个剂量组单次给药,其中为6例为空白对照;24例受试者分别接受2个剂量28 d连续给药,其中8例为空白对照组;分别于入组前、试验中和出组时若干时点收集血、尿样本以进行安全性评价。结果:尿NAG酶作为早期反映肾小管损害的敏感指标,其升高多为单独异常,不伴有其他肾功能指标具有临床意义的异常变化。无论单次给药组还是连续给药组,与空白对照组相比该指标的变化均无统计学意义(P>0.05)。结论:采用该指标进行肾脏安全性评价时,应建立严格、全面的质量控制体系,同时建议采用多指标综合评价的方法,以结果的相互验证为研究者提供更多的临床提示。Objective： To explore the reasonable application and evaluation thoughts of urinary NAG for kidney safety evaluation in an initial human clinical trial. Methods： A randomized,open label,blank control,single / multiple dose,and oral medication clinical trial was conducted. Healthy subjects（ n = 40） were randomized into 7 single dose groups,6 of them were in blank control group; 24 healthy subjects were randomized into 2 dose successive medication groups,8 of them were in blank control group. The blood and urine specimens were collected at various time points for safety evaluation. Results： As the sensitive indicator reflecting early kidney tubular injury,it was commonly manifested as independent increase without other clinically significant abnormal changes of kidney function. The difference between experimental and blank groups showed no statistically significance（ P 〉 0.05）. Conclusion： A strict and sound quality control system should be established when applying urinary NAG for kidney safety evaluation. Meanwhile,the comprehensive evaluation method with multiple indexes is recommended in order to provide more clinical suggestion for investigators based on mutual authentication between indexes.

关 键 词：首次健康人体试验 尿NAG酶 安全性评价 

分 类 号：R969[医药卫生—药理学]