Document Detail

The influence of the sennosides on absorption of glycyrrhetic acid in rats.
MedLine Citation:
PMID:  16204942     Owner:  NLM     Status:  MEDLINE    
In the course of our clinical studies of Kampo medicine (traditional Japanese medicines), we observed the pharmacokinetic interactions between two herbs. When Onpito (TJ-8117, Kampo medicine) containing licorice and rhubarb was administered orally to human subjects, we observed that the AUC(0-lim) and Cmax of glycyrrhetic acid (GA) in plasma were lower than those treated with other Kampo medicines containing licorice. In this study, we demonstrate the pharmacokinetic interactions of GA derived from glycyrrhizinic acid (GL) in licorice and anthraquinones derived from rhubarb. To our knowledge, this is the first report to investigate the pharmacokinetic interactions between two herbs. When GL was orally co-administrated to rats with a non-effective dose of sennoside A having purgative activity, the AUC(0-lim) and Cmax of GA decreased. In addition, sennoside A did not affect the metabolism of GL by the intestinal bacteria in vitro. In the examination using an in situ loop of rat colon, the remaining ratio of GA rose drastically by the co-administration of sennoside A, sennidin A and rhein. Observed inhibition activity of these anthraquinones on GA absorption depended on the concentration of the components added. The maximum inhibition ratio was approximately 75% by rhein, 60% by sennoside A and 25% by sennidin A. We conclude that the decrease of the pharmacokinetic parameters of GA in human plasma observed in the clinical study of TJ-8117 is attributable to an interactive action of absorption from the intestinal tract by anthraquinones contained in or derived from rhubarb.
Yasuharu Mizuhara; Yukiho Takizawa; Kazuhisa Ishihara; Takayuki Asano; Hirotaka Kushida; Takashi Morota; Yoshio Kase; Shuichi Takeda; Masaki Aburada; Masaaki Nomura; Koichi Yokogawa
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  28     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-05     Completed Date:  2006-02-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1897-902     Citation Subset:  IM    
Medicinal Evaluation Laboratory, Tsumura & Co; 3586 Yoshiwara, Ami-machi, Inasiki-gun, Ibaraki 300-1192, Japan.
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MeSH Terms
Anthraquinones / pharmacology*
Area Under Curve
Chromatography, High Pressure Liquid
Glycyrrhetinic Acid / analysis,  blood,  pharmacokinetics*
Immunoenzyme Techniques
Intestinal Absorption
Intestines / microbiology
Rats, Sprague-Dawley
Reg. No./Substance:
0/Anthraquinones; 471-53-4/Glycyrrhetinic Acid; 517-43-1/sennoside A&B

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