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The effect of piperine on midazolam plasma concentration in healthy volunteers, a research on the CYP3A-involving metabolism

Rezaee, Mohammad Mahdi, Kazemi, Sohrab, Kazemi, Mohammad Taghi, Gharooee, Saeed, Yazdani, Elham, Gharooee, Hoda, Shiran, Mohammad Reza, Moghadamnia, Ali Akbar·2014·DARU Journal of Pharmaceutical Sciences
DOI 10.1186/2008-2231-22-8
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Abstract

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±0.0 3 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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Metadata

Authors
Rezaee, M. M., Kazemi, S., Kazemi, M. T., Gharooee, S., Yazdani, E., Gharooee, H., Shiran, M. R., & Moghadamnia, A. A.
Venue
DARU Journal of Pharmaceutical Sciences
Publisher
Springer Science and Business Media LLC
Published
2014-01-07
Volume
22
Issue
1
ISSN
2008-2231
DOI
10.1186/2008-2231-22-8
Cited by
31
References
1
Language
en
Licence
creativecommons.org/licenses/by/2.0 (tdm)

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CoChat. (2026). Citation check: The effect of piperine on midazolam plasma concentration in healthy volunteers, a research on the CYP3A-involving metabolism. https://app.cochat.ai/papers/10.1186/2008-2231-22-8
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Rezaee, M. M., Kazemi, S., Kazemi, M. T., Gharooee, S., Yazdani, E., Gharooee, H., Shiran, M. R., & Moghadamnia, A. A. (2014). The effect of piperine on midazolam plasma concentration in healthy volunteers, a research on the CYP3A-involving metabolism. DARU Journal of Pharmaceutical Sciences. https://doi.org/10.1186/2008-2231-22-8

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