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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 investigate the reasonable application and evaluation of urinary NAG enzyme in the evaluation of renal safety in the first healthy human test. Methods: Randomized, open, blank control, single / multiple dose, oral administration of experimental design, 40 healthy subjects were randomized to a single dose of 7 doses, of which 6 were blank control; 24 patients The subjects received two doses of 28 consecutive days of administration, of which 8 were blank control group; were collected before and after the test and the group at a number of time points collected blood, urine samples for safety evaluation. Results: Urinary NAG enzyme as a sensitive indicator of early renal tubular damage, the rise of more than as a single abnormality, without other clinical indicators of abnormal changes in renal function. Compared with the blank control group, there was no significant difference in the index between the single administration group and the continuous administration group (P> 0.05). Conclusion: When using this index for renal safety evaluation, a strict and comprehensive quality control system should be established. At the same time, a multi-index comprehensive evaluation method should be established to provide more clinical tips for mutual recognition of the results.