title: The effects of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids in herb couple of Radix Aconiti Lateralis-Rhizoma Zingiberis.
abstract: BACKGROUND
  Radix Aconiti Lateralis (Fuzi in Chinese, derived from the lateral roots of Aconitum Carmichaeli Debx.) is widely used for the treatment of heart failure, internal cold, arthralgia, diarrhea and edema for thousands of years. It was usually prescribed in combination with Rhizoma Zingiberis (Ganjiang in Chinese, derived from the dry rhizome of Zingiber officinale Rosc.) to decrease toxicity and increase efficacy.
  
  
  OBJECTIVE
  In order to investigate the influence of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA), in Fuzi-Ganjiang herb couple, the comparative pharmacokinetics of six Aconitum alkaloids after oral administration of Fuzi and Fuzi-Ganjiang aqueous extract was carried out.
  
  
  METHODS
  A sensitive, specific and rapid LC-MS/MS method was developed to determine the six analytes in plasma. Then the rats were randomly divided into two groups and orally administered with Fuzi and Fuzi-Ganjiang aqueous extract. At designated time points after oral administration, the concentrations of the six Aconitum alkaloids in rat plasma were determined, and main pharmacokinetic parameters were investigated using 3P97 (Practical Pharmacokinetics Program Version 1.0).
  
  
  RESULTS
  Comparing with Fuzi group, both T1/2 and AUC0-t of AC and HA decreased (P<0.05), while T1/2, AUC0-t and Cmax of BAC, BHA increased (P<0.05) in Fuzi-Ganjiang group, which indicated that Ganjiang could promote the elimination of AC and HA and enhance the absorption of BAC, BHA and BMA.
  
  
  CONCLUSIONS
  The differences of pharmacokinetics of Aconitum alkaloids in rat plasma could support those of pharmacologics and toxicity in previous reports between Fuzi and Fuzi-Ganjiang herb couple. The results might be helpful in explaining the mechanism of combination of Fuzi-Ganjiang to decrease toxicity and increase efficacy.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, PR China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Peng
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Li
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Cui
authors.forename: Yong-xin
authors.initials: YX
authors.lastname: Zhang
authors.forename: Guang-Ming
authors.initials: GM
authors.lastname: Yang
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Wen
authors.forename: Bao-Chang
authors.initials: BC
authors.lastname: Cai
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D031841:Aconitum / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004224:Diterpenes; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D020939:Zingiber officinale / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008516:Medicine, Chinese Traditional / Q000379:methods; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000470:Alkaloids; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C479202:benzoylhypaconine; C575009:fuzi drug herbal; C047307:benzoylaconine; C058309:hypaconitine; C019470:mesaconitine; C085283:benzoylmesaconine; D000157:Aconitine