正常吸毒者口服脱毒舒胶囊Ⅰ期临床耐受性试验

Tolerance of Tuodushu capsule in normal drug addicts:A phaseⅠ clinical trial

目的:评价正常吸毒者口服脱毒舒胶囊的安全性和耐受性。方法:43名正常吸毒受试者进行单次及多次给药的耐受性试验。其中,单次给药者31人,经筛选合格后随机分配到7个剂量组(1、2、3、4、5、6和7粒组)。多次给药者12人,男女各半,分为3粒组和4粒组,连续给药6d,前3d1d2次,1次3(或4)粒;后3d1d2次,1次2粒。观察记录给药前后不同时间的体格检查、生命体征、心电图、血常规、尿常规、血液生化等指标。结果:给药后体格检查、体征未见有临床意义的改变。实验室检查中单次组共有4组(3、4、5、6粒给药组)的BUN值和两组(3、7粒给药组)的Cr值试验前后变化有统计学意义(P<0.05),多次给药两组的BUN值和Cr值试验前后变化都有统计学意义(P<0.05);少数病例的CK值变化有临床意义,但该组均数前后变化分析无统计学差异。试验中不良事件均为轻中度且为一过性,未见严重不良事件发生。结论:脱毒舒胶囊单次给药1～7粒,受试者均可耐受;多次给药(前3d早晚各4粒,后3d早晚各2粒)受试者可以耐受。推荐II期临床研究用药剂量为多次给药,疗程6d,前3d早晚各4(或3)粒,后3d早晚各2(或1)粒,但需注意受试者睡眠、饮食、心肌酶和大小便等的变化。

AIM： To assess the safety and tolerance of Tuodushu capsule in normal drug addictive volunteers. METHODS： 43 subjects were enrolled in the non-controlled single-dose trial or multiple-dose trial. Thirty-one subjects were randomized into 7 dose groups （1, 2, 3, 4, 5, 6 and 7 capsules group） for single- dose triM. Twelve subjects, six males and six females, equally divided into two treatment groups （3 capsules or 4 capsules group）, were orally given 3 or 4 capsules per times, b. i.d. in the first 3 days and 2 capsules per times, b.i.d, in the last 3 days for muhiple-dose trial. The physical examination, vital signs, electro- cardiogram, routine blood tests, routine urine tests, and blood biochemical tests were conducted on sched- ule and statistically evaluated. RESULTS： There were no significant clinical changes in physical examination and vital signs after administration. In single-dose trial, statistically significance （ P 〈 0.05） in BUN in 4 groups （3, 4, 5, 6 capsules group） and Cr in 2 groups （3, 7 capsules group） were found. In multiple-dose trial, statistically significances （ P 〈 0.05） in BUN and Cr between two gTOUpS were observed. There were significant clinical changes in CK in a small number of cases, but no differences between cases. All adverse events were mild to moderate and transient and no serious adverse events were found in the trial. CONCLUSION： Tuodushu capsule is safe and well tolerated in normal drag addictive volunteers at dose of 1-7 capsules once daily. In addition, the multiple-dose level of 4 capsules per times, b. i.d. in the first 3 days and 2 capsules per times, b. i.d. in the last 3 days is assessed as safe and well tolerated. The recommended oral dosage regimen for phase Ⅱ clinical trial is 3 or 4 capsules per times, b.i.d, in the first 3 days and 1 or 2 capsules per times, b. i. d. in the last 3 days for multiple-dose trial. Attention should be paid to the changes in sleep, diet, Cr and defecation.