title: Assessment of the effects of Radix bupleuri and vinegar-baked Radix bupleuri on cytochrome 450 activity by a six-drug cocktail approach.
abstract: OBJECTIVE
  To assess the effects of Radix Bupleuri and vinegar-baked Radix Bupleuri on cytochrome 450 activity of rats.
  
  
  METHODS
  Six probe drugs (caffeine, midazolam, dextromethorphan, tolbutamide, omeprazole, chlorzoxazone) were simultaneously given to rats after different dosing of Radix Bupleuri or vinegar-baked Radix Bupleuri for seven days. The plasma concentrations of the six probes were measured by high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS/MS) and their corresponding pharmacokinetic parameters were calculated.
  
  
  RESULTS
  The AUC and T1/2 of midazolam, dextromethorphan and chlorzoxazone decreased significantly (P < 0.05) in rats after different dosing of Radix Bupleuri or vinegar-baked Radix Bupleuri for seven days. Treatment of Radix Bupleuri decreased T1/2 and AUC of omeprazole, but treatment of vinegar-baked Radix Bupleuri with normal dose did not change the pharmacokinetics of omeprazole. The pharmacokinetics of tolbutamide in all vinegar-baked Radix Bupleuri-treated rats showed no statistically significant difference (P > 0.05) from that of controlled rats, however, treatment of Radix Bupleuri decreased tolbutamide T1/2. The pharmacokinetics of caffeine in all Radix Bupleuri or vinegar-baked Radix Bupleuri-treated rats showed no statistically significant difference (P > 0.05) from that of controlled rats.
  
  
  CONCLUSIONS
  The Radix Bupleuri and vinegar-baked Radix Bupleuri have different effects on the CYP2C9 and CYP2C19. Radix Bupleuri and vinegar-baked Radix Bupleuri have strong induction effects on the CYP2E1, CYP2D6 and CYP3A4, however, have no impact on CYP1A2. The reason of different therapeutic effects of Radix Bupleuri and vinegar-baked Radix Bupleuri extract may be the different effects of Radix Bupleuri and vinegar-baked Radix Bupleuri on the CYP2C9 and CYP2C19.
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Yin
authors.initials: Y
authors.lastname: Huang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Liu
authors.forename: Zun-Jian
authors.initials: ZJ
authors.lastname: Zahng
mesh_terms: D000818:Animals; D029972:Bupleurum / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System