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Research ArticleArticle

Hepatobiliary Excretion of Silibinin in Normal and Liver Cirrhotic Rats

Jhy-Wen Wu, Lie-Chwen Lin, Shih-Chieh Hung, Chi-Hung Lin, Chin-Wen Chi and Tung-Hu Tsai
Drug Metabolism and Disposition March 2008, 36 (3) 589-596; DOI: https://doi.org/10.1124/dmd.107.017004
Jhy-Wen Wu
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Lie-Chwen Lin
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Shih-Chieh Hung
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Chi-Hung Lin
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Chin-Wen Chi
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Tung-Hu Tsai
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Abstract

Silibinin is the main biologically active flavonolignan extracted from the seeds and fruits of milk thistle and has potential efficacy in the treatment of liver disease. The aim of the present study was to examine the hepatobiliary excretion of silibinin and its effect on dimethylnitrosamine (DMN)-induced liver cirrhosis. The experiments were divided into five groups: 10, 30, and 50 mg/kg silibinin alone, 30 mg/kg silibinin coadministered with cyclosporin A (CsA), and 50 mg/kg silibinin with liver cirrhosis induced by DMN. The data indicated that silibinin had dose-related pharmacokinetics in the dose ranges of 10 to 50 mg/kg. All of the unconjugated or total (unconjugated + conjugated) silibinin concentrations in the bile were significantly higher than those in plasma at the sampling time points at each dose, suggesting active hepatobiliary excretion. When coadministered with CsA, the area under the concentration versus time curve (AUC) in bile was significantly decreased. This result suggested that the active silibinin efflux might be partially inhibited by P-glycoprotein. In the DMN-induced liver cirrhotic rats, the AUC of plasma unconjugated silibinin was reduced by 53%; however, total silibinin was increased by 182%. These results together suggest that the phase II conjugative reaction of silibinin was blocked by treatment with DNM.

Footnotes

  • Funding for this study was provided in part by research Grants: NSC96-2113-M-010-003-MY3 and NSC96-2628-B-010-006-MY3 from the National Science Council; TCH 95004-62-170 from Taipei City Hospital; and V96E2-009 from Taipei Veterans General Hospital, Taiwan.

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

  • doi:10.1124/dmd.107.017004.

  • ABBREVIATIONS: P-gp, P-glycoprotein; CsA, cyclosporin A; DMN, dimethylnitrosamine; HPLC, high-performance liquid chromatography; AUC, area under the concentration versus time curve.

    • Received June 1, 2007.
    • Accepted November 27, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 36 (3)
Drug Metabolism and Disposition
Vol. 36, Issue 3
1 Mar 2008
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Research ArticleArticle

Hepatobiliary Excretion of Silibinin in Normal and Liver Cirrhotic Rats

Jhy-Wen Wu, Lie-Chwen Lin, Shih-Chieh Hung, Chi-Hung Lin, Chin-Wen Chi and Tung-Hu Tsai
Drug Metabolism and Disposition March 1, 2008, 36 (3) 589-596; DOI: https://doi.org/10.1124/dmd.107.017004

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Research ArticleArticle

Hepatobiliary Excretion of Silibinin in Normal and Liver Cirrhotic Rats

Jhy-Wen Wu, Lie-Chwen Lin, Shih-Chieh Hung, Chi-Hung Lin, Chin-Wen Chi and Tung-Hu Tsai
Drug Metabolism and Disposition March 1, 2008, 36 (3) 589-596; DOI: https://doi.org/10.1124/dmd.107.017004
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