Some studies showed that piperine (the alkaloid of piper nigrum) can change the activities of microsomal enzymes.\r\nMidazolam concentration is applied as a probe to determine the CYP3A enzyme activity. This study was done to\r\ndetermine piperine pretreatment role on midazolam plasma concentration.\r\nTwenty healthy volunteers (14 men and 6 women) received oral dose of piperine (15 mg) or placebo for three days\r\nas pretreatment and midazolam (10 mg) on fourth day of study and the blood samples were taken at 0.5, 2.5 and\r\n5 h after midazolam administration. The midazolam plasma levels were assayed using HPLC method (C18 analytical\r\ncolumn, 75:25 methanol:water as mobile phase, UV detector at 242 nm wavelength and diazepam as internal standard).\r\nData were fit in a ââ?¬Å?one-compartment PK modelââ?¬Â using P-Pharm 1.5 software and analyzed under statistical tests.\r\nThe mean Ã?±SD of the age and body mass index were 24.3 Ã?± 1.83 years (range: 21ââ?¬â??28 years) and 23.46Ã?± 2.85,\r\nrespectively. The duration of sedation in piperine receiving group was greater that the placebo group (188Ã?±59 vs.\r\n102Ã?±43 min, p<0.0001). Half-life and clearance of midazolam were higher in piperine pretreatment group compared to\r\nplacebo [1.88Ã?±0.03 vs. 1.71Ã?± 0.04 h (p<0.0001) and 33.62 Ã?± 0.4 vs. 37.09 Ã?± 1.07 ml/min (p<0.0001), respectively].\r\nAccording to the results, piperine can significantly increases half-life and decreases clearance of midazolam compared\r\nto placebo. It is suggested that piperine can demonstrate those effects by inhibition CYP3A4 enzyme activity in liver\r\nmicrosomal system.
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