title: Influences of Re Du Ning Injection, a traditional Chinese medicine injection, on the CYP450 activities in rats using a cocktail method.
abstract: BACKGROUND
  Re Du Ning Injection (RDN), a traditional Chinese medicine injection, is made from the extracts of Lonicerae japonicae flos (LJF), Artemisiae annuae herba (AAH) and Gardeniae fructus (GF). Since last decade, RDN has been widely used in China for the treatment of fever, inflammation, allergy and viral infection.
  
  
  OBJECTIVE
  To elucidate the potential influences of RDN on the activities of four cytochrome P450 (CYP) isozymes in rats (CYP1A2, CYP2C11, CYP2D1 and CYP3A1/2) by "cocktail method".
  
  
  METHODS
  A sensitive and specific LC-MS method capable of simultaneous quantification of four substrates and their metabolites in rat plasma was developed and validated. Relative activity estimation of four isozymes was carried out by comparing plasma pharmacokinetics of substrates and their metabolites (phenacetin/ paracetamol for CYP1A2, tolbutamide/4-hydroxytolbutamide for CYP2C11, dextromethorphan/ dextrorphan for CYP2D1 and dapsone/N-acetyl dapsone for CYP3A1/2) between control and RDN treatment groups.
  
  
  RESULTS
  Compared with control group, RDN at different levels could increase the total amount of tolbutamide, dextromethorphan and dapsone absorbed into blood, while decrease the total amount of phenacetin absorbed into blood at low and medium dosage and increase it at high dosage.
  
  
  CONCLUSIONS
  RDN could inhibit the activities of CYP2C11, CYP2D1 and CYP3A1/2, induce the activity of CYP1A2 at low and medium dosage but inhibit it at high dosage. The results indicated that drug co-administrated with RDN may need dose adjustment.
authors: Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China; State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China.
authors: Ting
authors: T
authors: Geng
authors: Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China; State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China.
authors: Haihong
authors: H
authors: Si
authors: Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China; China Pharmaceutical University, Nanjing 210009, China.
authors: Danyu
authors: D
authors: Kang
authors: Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China; State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China.
authors: Yanjing
authors: Y
authors: Li
authors: Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China; State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China.
authors: Wenzhe
authors: W
authors: Huang
authors: Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China; State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China.
authors: Gang
authors: G
authors: Ding
authors: State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China.
authors: Zhenzhong
authors: Z
authors: Wang
authors: State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China.
authors: Yu'an
authors: Y
authors: Bi
authors: Jiangsu Kanion Modern Chinese Medicine Institute, Nanjing 210017, China; State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China.
authors: Hong
authors: H
authors: Zhang
authors: State Key Laboratory of Pharmaceutical New-Tech for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; National Enterprise Technology Center, National Post-doctoral Research Workstation, Jiangsu Enterprise Academician Workstation, Lianyungang 222001, China. Electronic address: kanionxw2010@126.com.
authors: Wei
authors: W
authors: Xiao
mesh_terms: D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D057230:Limit of Detection; D008297:Male; D008516:Medicine, Chinese Traditional; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004365:Drugs, Chinese Herbal; D007527:Isoenzymes; D004364:Pharmaceutical Preparations; C000596355:reduning; D003577:Cytochrome P-450 Enzyme System
keywords: Cocktail; Cytochrome P450; Iridoid glycosides; Pharmacokinetics; Phenolic acids; Re Du Ning Injection