天然维生素E对CYP3A4活性影响的体内研究

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (8): 911-915.

天然维生素E对CYP3A4活性影响的体内研究

张松波^1,2, 段娟³, 闾四平¹, 尚云峰¹, 宋旭日¹, 周宏灏²

¹岳阳职业技术学院,岳阳 414000,湖南;
²中南大学临床药理研究所,长沙 410078,湖南;
³湖南省血防所附属医院,岳阳 414000,湖南

收稿日期:2010-08-11 修回日期:2010-08-14 出版日期:2010-08-26 发布日期:2020-09-17
通讯作者: 周宏灏,男,教授,研究方向:遗传药理学与药物基因组学。Tel: 0731-4805380 E-mail: hhzhou2003@163.com
作者简介:张松波,硕士,讲师,研究方向:药物基因组学及临床药理。Tel: 13973067097 E-mail: zsb8283271@163.com

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

ZHANG Song-bo^1,2, DUAN Juan³, LV Si-ping¹, SHANG Yun-feng¹, SONG Xu-ri¹, ZHOU Hong-hao²

¹ Yueyang Vocational Technical College,Yueyang 414000, Hunan,China;
²Institute of Clinical Pharmacology,Central South University, Changsha 410078, Hunan, China;
³Affiliated Xiangyue Hospital, Hunan Provincial Dispensary of Schistosomiasis,Yueyang 414000, Hunan, China

Received:2010-08-11 Revised:2010-08-14 Online:2010-08-26 Published:2020-09-17

摘要/Abstract

摘要： 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E 600 mg/d,另一组不服药,连续 14 d。在第15天两组均口服咪达唑仑 7.5 mg,在0、0.25、0.5、0.75、1、1.5、2、2.5、3、4、6、8、12、24 h 采外周静脉血 5 mL,洗脱4周交叉进行下阶段试验。采血后 0.5 h 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AUC_{0-24 h}和峰浓度C_max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。

关键词: 天然维生素E, CYP3A4, 咪达唑仑

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

中图分类号:

R969

张松波, 段娟, 闾四平, 尚云峰, 宋旭日, 周宏灏. 天然维生素E对CYP3A4活性影响的体内研究[J]. 中国临床药理学与治疗学, 2010, 15(8): 911-915.

ZHANG Song-bo, DUAN Juan, LV Si-ping, SHANG Yun-feng, SONG Xu-ri, ZHOU Hong-hao. Effects of regular consumption of RRR-tocopherol on the activity of CYP3A 4 in vivo[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(8): 911-915.

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