title: Effects of notoginsenoside R1 on CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 activities in rats by cocktail probe drugs.
abstract: BACKGROUND
  Notoginsenoside R1 (NGR1) is the main component with cardiovascular activity in Panax notoginseng (Burk.) F. H. Chen, an herbal medicine that is widely used to enhance blood circulation and dissipate blood stasis.
  
  
  OBJECTIVE
  The objective of this study is to investigate NGR1's effects on CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 activities in rats in vivo through the use of the Cytochrome P450 (CYP450) probe drugs.
  
  
  METHODS
  After pretreatment with NGR1 or physiological saline, the rats were administered intraperitoneally with a mixture solution of cocktail probe drugs containing caffeine (10 mg/kg), tolbutamide (15 mg/kg), metoprolol (20 mg/kg), and dapsone (10 mg/kg). The bloods were then collected at a set of time-points for the ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis.
  
  
  RESULTS
  NGR1 was shown to exhibit an inhibitory effect on CYP1A2 by increased caffeine Cmax (43.13%, p < 0.01) and AUC0 - ∞ (40.57%, p < 0.01), and decreased CL/F (62.16%, p < 0.01) in the NGR1-treated group compared with those of the control group, but no significant changes in pharmacokinetic parameters of tolbutamide, metoprolol, and dapsone were observed between the two groups, indicating that NGR1 had no effects on rat CYP2C11, CYP2D1, and CYP3A1/2.
  
  
  CONCLUSIONS
  When NGR1 is co-administered with drugs that are metabolized by CYP1A2, the pertinent potential herb-drug interactions should be monitored.
authors.affiliation: a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , PR China and.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yin
authors.affiliation: a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , PR China and.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , PR China and.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: b Department of Pharmacy , The Third Affiliated Hospital, Harbin Medical University , Harbin , PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.affiliation: a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , PR China and.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhao
authors.affiliation: a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , PR China and.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Liu
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D003580:Cytochromes / Q000037:antagonists & inhibitors*; D036145:Ginsenosides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D008297:Male; D053723:Panax notoginseng / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood*; D017208:Rats, Wistar; D039181:Steroid 16-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D013379:Substrate Specificity
chemical_list: D003580:Cytochromes; D036145:Ginsenosides; D004364:Pharmaceutical Preparations; D000429:Alcohol Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C017170:Cyp1a2 protein, rat; C504568:Cyp2d1 protein, rat; C465260:Cyp3a2 protein, rat; C465138:Cyp3a23-3a1 protein, rat; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; C072936:notoginsenoside R1
keywords: Caffeine; UPLC-MS/MS; cytochrome P450; daspone; metoprolol; pharmacokinetics; tolbutamide