The effect of piperine on midazolam plasma concentration in healthy volunteers, a research on the CYP3A-involving metabolism.
The effect of piperine on midazolam plasma concentration in healthy volunteers, a research on the CYP3A-involving metabolism.
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DOI：
10.1186/2008-2231-22-8
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发表时间：
2014-01-07
期刊：
影响因子：
--
通讯作者：
Moghadamnia AA
中科院分区：
文献类型：
--
作者：
Rezaee MM;Kazemi S;Kazemi MT;Gharooee S;Yazdani E;Gharooee H;Shiran MR;Moghadamnia AA
胡椒碱是胡椒属植物胡椒的生物碱，有研究表明胡椒碱能改变微粒体酶的活性。咪达唑仑浓度用作探针，以测定CYP 3A酶活性。本研究旨在探讨胡椒碱预处理对咪达唑仑血药浓度的影响。20名健康志愿者（14名男性和6名女性）口服胡椒碱（15 mg）或安慰剂3 d作为研究前，并在研究的第4天口服咪达唑仑（10 mg），并在咪达唑仑给药后0.5、2.5和5 h采集血样。采用HPLC法（C18分析柱，75：25甲醇：水作为移动的相，242 nm波长处的UV检测器，地西泮作为内标物）测定咪达唑仑的血浆水平。使用P-Pharm 1.5软件将数据拟合在“一室PK模型”中，并在统计学检验下进行分析。年龄和体重指数的平均值±SD分别为24.3 ± 1.83岁（范围：21-28岁）和23.46± 2.85。胡椒碱组镇静持续时间较安慰剂组长（188±59 vs. 102±43 min，p<0.0001）。胡椒碱预处理组咪达唑仑的半衰期和清除率高于安慰剂组[分别为1.88±0.03 vs. 1.71± 0.04 h（p<0.0001）和33.62 ± 0.4 vs. 37.09 ± 1.07 ml/min（p<0.0001）]。结果表明，与安慰剂相比，胡椒碱能显著延长咪达唑仑的半衰期，降低清除率。提示胡椒碱可能通过抑制肝微粒体系统CYP 3A 4酶活性而发挥上述作用。
Some studies showed that piperine (the alkaloid of piper nigrum) can change the activities of microsomal enzymes. Midazolam concentration is applied as a probe to determine the CYP3A enzyme activity. This study was done to determine piperine pretreatment role on midazolam plasma concentration. Twenty healthy volunteers (14 men and 6 women) received oral dose of piperine (15 mg) or placebo for three days as pretreatment and midazolam (10 mg) on fourth day of study and the blood samples were taken at 0.5, 2.5 and 5 h after midazolam administration. The midazolam plasma levels were assayed using HPLC method (C18 analytical column, 75:25 methanol:water as mobile phase, UV detector at 242 nm wavelength and diazepam as internal standard). Data were fit in a “one-compartment PK model” using P-Pharm 1.5 software and analyzed under statistical tests. The mean ±SD of the age and body mass index were 24.3 ± 1.83 years (range: 21–28 years) and 23.46± 2.85, respectively. The duration of sedation in piperine receiving group was greater that the placebo group (188±59 vs. 102±43 min, p<0.0001). Half-life and clearance of midazolam were higher in piperine pretreatment group compared to placebo [1.88±0.03 vs. 1.71± 0.04 h (p<0.0001) and 33.62 ± 0.4 vs. 37.09 ± 1.07 ml/min (p<0.0001), respectively]. According to the results, piperine can significantly increases half-life and decreases clearance of midazolam compared to placebo. It is suggested that piperine can demonstrate those effects by inhibition CYP3A4 enzyme activity in liver microsomal system.
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影响因子：
3.9
作者：
Klees, TM;Sheffels, P;Kharasch, ED
通讯作者：
Kharasch, ED
影响因子：
37.8
作者：
Darbar, D;Fromm, MF;Roden, DM
通讯作者：
Roden, DM
影响因子：
158.5
作者：
KREEK, MJ;GARFIELD, JW;GIUSTI, LM
通讯作者：
GIUSTI, LM
影响因子：
3.9
作者：
Lalovic, B;Phillips, B;Shen, DD
通讯作者：
Shen, DD
DOI：
10.1124/jpet.102.034728
发表时间：
2002-08-01
影响因子：
3.5
作者：
Bhardwaj, RK;Glaeser, H;Fromm, MF
通讯作者：
Fromm, MF