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Research ArticleArticle

Absorption and Disposition of Scutellarin in Rats: A Pharmacokinetic Explanation for the High Exposure of Its Isomeric Metabolite

Chunying Gao, Xiaoyan Chen and Dafang Zhong
Drug Metabolism and Disposition November 2011, 39 (11) 2034-2044; DOI: https://doi.org/10.1124/dmd.111.040550
Chunying Gao
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Xiaoyan Chen
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Dafang Zhong
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Abstract

Scutellarin or scutellarein-7-O-glucuronide (S-7-G) is a flavonoid used in the treatment of cardiovascular diseases. After oral administration to humans, S-7-G can hardly be detected, whereas its isomeric metabolite [scutellarein-6-O-glucuronide (S-6-G)] dominates in plasma. A preliminary study in rats also revealed a low bioavailability of S-7-G, as well as a high plasma concentration of S-6-G. Therefore, the present study tried to explore the possible causes of the unusual pharmacokinetics of scutellarin in humans through investigating the absorption and disposition of S-7-G in rats. After oral administration to rats, S-7-G was largely hydrolyzed in the intestinal tract and was absorbed as aglycone. While passing through the intestinal wall, aglycone was extensively glucuronidated into S-7-G and S-6-G (approximately 20:1), which subsequently entered the mesenteric blood (approximately 15:1). However, because S-7-G exhibited more rapid uptake in hepatocytes, was glucuronidated at a 2.7-fold higher rate in the liver, and was excreted in greater amounts through bile and urine than S-6-G, the S-7-G/S-6-G ratio eventually declined to approximately 1.5:1 in the systemic circulation. Findings revealed that S-7-G cannot be absorbed directly; S-7-G and S-6-G in the body were mostly generated from aglycone in the intestinal wall; a larger amount of S-7-G than S-6-G entered the mesenteric blood at the absorption stage, but the gap between them shrank quickly mainly because of the higher hepatic first-pass elimination of S-7-G. These findings in rats are of great value as reference for further study to accurately interpret the pharmacokinetics of S-7-G in humans.

Footnotes

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.111.040550.

  • ABBREVIATIONS:

    S-7-G
    scutellarin, scutellarein-7-O-glucuronide
    S-6-G
    isoscutellarin, scutellarein-6-O-glucuronide
    UDPGA
    uridinediphosphateglucuronic acid
    UGT
    UDP glucuronyltransferase
    RLM
    rat liver microsomes
    HBSS
    Hanks' balanced salt solution
    UPLC-Q/TOF MS
    ultraperformance liquid chromatography-quadrupole/time-of-flight mass spectrometry
    LC-MS/MS
    liquid chromatography-tandem mass spectrometry
    AUC
    area under curve
    Papp
    apparent permeability
    MDF
    mass defect filter
    PBS
    phosphate-buffered saline
    HPLC
    high-performance liquid chromatography
    C/M ratio
    cell/medium concentration ratio
    CE
    collision energy
    S-6,7-diG
    6,7-O-diglucuronide scutellarein
    MRT
    mean residence time.

  • Received May 12, 2011.
  • Accepted August 2, 2011.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 39 (11)
Drug Metabolism and Disposition
Vol. 39, Issue 11
1 Nov 2011
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Research ArticleArticle

ABSORPTION AND DISPOSITION OF SCUTELLARIN IN RATS

Chunying Gao, Xiaoyan Chen and Dafang Zhong
Drug Metabolism and Disposition November 1, 2011, 39 (11) 2034-2044; DOI: https://doi.org/10.1124/dmd.111.040550

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Research ArticleArticle

ABSORPTION AND DISPOSITION OF SCUTELLARIN IN RATS

Chunying Gao, Xiaoyan Chen and Dafang Zhong
Drug Metabolism and Disposition November 1, 2011, 39 (11) 2034-2044; DOI: https://doi.org/10.1124/dmd.111.040550
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