天然维生素E对CYP3A4活性影响的体内研究

目的：阐明天然维生素E在体内对CYP3A4活性的影响。方法：12名健康男性志愿者,随机分两组,采用两阶段双周期交叉设计,一组口服天然维生素E600mg/d,另一组不服药,连续14d。在第15天两组均口服咪达唑仑7.5mg,在0、0.25、0.5、0.75、1、1.5、2、2.5、3、4、6、8、12、24h采外周静脉血5mL,洗脱4周交叉进行下阶段试验。采血后0.5h内进行离心和分离血浆,运用HPLC-MS-MS分别测定血浆中咪达唑仑总药物浓度、1-OH咪达唑仑药物浓度,分析比较不同处理组间药代动力学参数的差异。结果：天然维生素E服用组与对照组咪达唑仑及其代谢产物1-OH咪达唑仑的血浆药物浓度变化相近。天然维生素E服用组与对照组之间咪达唑仑及其代谢产物1-OH咪达唑仑的曲线下面积AUC0-24h和峰浓度Cmax数据相近（P〉0.05）。结论：在本试验中服用天然维生素E并未影响CYP3A4的体内活性。

Effects of regular consumption of RRR-tocopherol on the activity of CYP3A 4 in vivo

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 AUC0-24 h（P=0.850）and Cmax（P=0.057）of midazolam and AUC0-24 h（P=0.967）and Cmax（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.