The effects of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids in herb couple of Radix Aconiti Lateralis−Rhizoma Zingiberis

• Published in: Journal of ethnopharmacology 2013-07, Vol.148 (2), p.579-586
• Main Authors: Peng, Wen-Wen, Li, Wen, Li, Jun-Song, Cui, Xiao-Bing, Zhang, Yong-xin, Yang, Guang-Ming, Wen, Hong-Mei, Cai, Bao-Chang
• Format: Article
• Language: English
• Subjects: absorption; Aconitine - analogs & derivatives; Aconitine - chemistry; Aconitine - pharmacokinetics; Aconitine - pharmacology; Aconitum - chemistry; Aconitum alkaloids; Aconitum carmichaelii; alkaloids; Alkaloids - chemistry; Alkaloids - pharmacokinetics; Alkaloids - pharmacology; Animals; Area Under Curve; bacterial artificial chromosomes; butylated hydroxyanisole; Chromatography, High Pressure Liquid - methods; cold; diarrhea; Diterpenes; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacokinetics; Drugs, Chinese Herbal - pharmacology; edema; heart failure; LC−MS/MS; Male; Mass Spectrometry - methods; Medicine, Chinese Traditional - methods; oral administration; Pharmacokinetic; pharmacokinetics; Plant Extracts - chemistry; Plant Extracts - pharmacokinetics; Plant Extracts - pharmacology; Radix Aconiti Lateralis; Random Allocation; Rats; Rats, Sprague-Dawley; Rhizoma Zingiberis; Rhizome - chemistry; roots; Tandem Mass Spectrometry - methods; toxicity; Zingiber officinale; Zingiber officinale - chemistry
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2013.04.056

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. 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. 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). Comparing with Fuzi group, both T1/2 and AUC0−t of AC and HA decreased (P