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Xenobiotica
the fate of foreign compounds in biological systems
Volume 43, 2013 - Issue 3
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Animal Pharmacokinetics and Metabolisms

Effects of single or repeated silymarin administration on pharmacokinetics of risperidone and its major metabolite, 9-hydroxyrisperidone in rats

, , , , , & show all
Pages 303-310 | Received 25 Jul 2012, Accepted 13 Sep 2012, Published online: 04 Dec 2012
 

Abstract

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 Cmax 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 Cmax 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 AUC0-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.

Acknowledgements

This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (NCRC program: 2012-0000952, Basic Science Research Program: 2012-004439).

Declaration of interest

The authors report no conflicts of interest. All the authors are responsible for the content of the paper.

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