摘要
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.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2009年第11期1286-1291,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics