Abstract: 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 singledose trial.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 multiple-dose trial.The physical examination, vital signs, electrocardiogram, routine blood tests, routine urine tests, and blood biochemical tests were conducted on schedule 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 groups 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 drug 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.

Key words: Tuodushu capsule, single-dose, multiple-dose, tolerance test