Abstract: AIM: To investigate the effect of regular consumption of RRR-α-tocopherol on the activity of CYP3A4 in vivo.METHODS: In a two-stage doubly periodic cross-over study, 12 healthy volunteers,who were randomly divided into two groups, ingested RRR-α-tocopherol 600 mg each day or placebo(control) for 14 days. On day 15, a single 7.5 mg dose of midazolam was administered by all the volunteers and 5 mL peripheral vein blood of each one was taken at 0,0.25,0.5,0.75,1,1.5,2,2.5,3,4,6,8,12,24 h. Plasma concentrations of midazolam,1-OH midazolam were determined by HPLC-MS-MS after centrifugation and blood plasma separation. The difference of pharmacokinetic parameters of every control groups were compared and analyzed.RESULTS: The AUC_{0-24 h} (P=0.850) and C_max (P=0.057) of midazolam and AUC_{0-24 h} (P=0.967) and C_max (P=0.096) of 1-OH midazolam showed no difference between two groups.CONCLUSION: Even 600 mg RRR-α-tocopherol, taken daily for 2 weeks, we failed to find any influence on the disposition of midazolam.

Key words: RRR-α-tocopherol , Cytochrome P3A4, Midazolam