title: Effect of Evodiamine on CYP Enzymes in Rats by a Cocktail Method.
abstract: The aim of this study was to assess the influence of evodiamine on the activities of the drug-metabolizing enzymes cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 in rats. The activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 were measured using specific probe drugs. After pretreatment for 1 week with evodiamine or physiological saline (control group) by oral administration, probe drugs phenacetin (5.0 mg/kg; CYP1A2 activity), tolbutamide (1.0 mg/kg; CYP2C9 activity), omeprazole (10 mg/kg; CYP2C19 activity), metoprolol (20 mg/kg; CYP2D6 activity) and midazolam (10 mg/kg; CYP3A4 activity) were administered to rats by oral administration. The blood was then collected at different times for ultra-performance liquid chromatography-tandem mass spectrometry analysis. The data showed that evodiamine exhibits an inhibitory effect on CYP1A2, CYP2C9 and CYP2D6 by increasing t(1/2), Cmax and AUC(0-∞), and decreasing CL/F compared with those of the control group. However, no significant changes in CYP2C19 and CYP3A4 activities were observed. In conclusion, the results indicated that evodiamine could inhibit CYP1A2, CYP2C9 and CYP2D6, which may affect the disposition of medicines primarily dependent on these pathways. Our work may be the basis of related herb-drug interactions in the clinic.
authors.affiliation: The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, PR China.
authors.forename: You-ting
authors.initials: YT
authors.lastname: Zhang
authors.forename: Da-feng
authors.initials: DF
authors.lastname: Zhang
authors.forename: Ni-yun
authors.initials: NY
authors.lastname: Ge
authors.forename: Guang-hui
authors.initials: GH
authors.lastname: Zhu
authors.forename: Cong
authors.initials: C
authors.lastname: Hao
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rui-jie
authors.initials: RJ
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D041743:Herb-Drug Interactions; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008790:Metoprolol / Q000097:blood / Q000493:pharmacokinetics; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics; D009853:Omeprazole / Q000097:blood / Q000493:pharmacokinetics; D010615:Phenacetin / Q000097:blood / Q000493:pharmacokinetics; D011799:Quinazolines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D011799:Quinazolines; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; C049639:evodiamine; D010615:Phenacetin; D008790:Metoprolol; D009853:Omeprazole; D008874:Midazolam