Document Detail


Effects of single or repeated silymarin administration on pharmacokinetics of risperidone and its major metabolite, 9-hydroxyrisperidone in rats.
MedLine Citation:
PMID:  23205514     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
1. The interactions between herbal dietary supplements and therapeutic drugs have emerged as an important issue and P-glycoprotein (P-gp) has been reported as one of the significant factors of these interactions. 2. The objective of this article is to examine the effects of single and repeated administrations of silymarin on pharmacokinetics of a P-gp substrate, risperidone, and its major metabolite, 9-hydroxyrisperidone, in rats. 3. To determine the plasma levels of risperidone and 9-hydroxyrisperidone in rats, a HPLC method was developed using a liquid-liquid acid back extraction. When risperidone (6 mg/kg) was co-administered with silymarin (40 mg/kg) to rats orally, the C(max) of 9-hydroxyrisperidone was significantly increased to1.3-fold (p < 0.05), while the other pharmacokinetic parameters did not show any significant differences. Expanding the experiment where rats were repeatedly administered with silymarin for 5 days prior to giving risperidone, the C(max) of risperidone and 9-hydroxyrisperidone were significantly increased to 2.4-fold (p < 0.001) and 1.7-fold (p < 0.001), respectively, and the AUC(0-t), as well to 1.7-fold (p < 0.05) and 2.1-fold (p < 0.01), respectively. 4. The repeated exposures of silymarin, compared to single administration of silymarin, increased oral bioavailability and affected the pharmacokinetics of risperidone and 9-hydroxyrisperidone, by inhibiting P-gp.
Authors:
Kyoung Sin Lee; Song Wha Chae; Joon Hee Park; Jung Hyun Park; Jong Min Choi; Sandy Jeong Yeon Rhie; Hwa Jeong Lee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-4
Journal Detail:
Title:  Xenobiotica; the fate of foreign compounds in biological systems     Volume:  -     ISSN:  1366-5928     ISO Abbreviation:  Xenobiotica     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1306665     Medline TA:  Xenobiotica     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Center for Cell Signaling & Drug Discovery Research, Division of Life and Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University , Seoul , Korea.
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