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Effect of Silymarin Supplement on the Pharmacokinetics of Rosuvastatin

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Abstract

Objectives

To evaluate the effect of silymarin on the pharmacokinetics of rosuvastatin in systems overexpressing OATP1B1 or BCRP transporters and in healthy subjects.

Materials and Methods

The concentration-dependent transport of rosuvastatin and the inhibitory effect of silymarin were examined in vitro in OATP1B1-expressing oocytes and MDCKII-BCRP cells. For in vivo assessment, eight healthy male volunteers, divided into two groups, were randomly assigned to receive placebo or silymarin (140 mg) three times per day for 5 days. On day 4, all subjects received rosuvastatin (10 mg, 8 am) 1 h after the placebo or silymarin administration. A series of blood samples were collected for 72 h, and the plasma concentration of rosuvastatin was determined using LC-MS/MS.

Results

Based on the concentration dependency of rosuvastatin transport in the OATP1B1 and BCRP overexpression systems, rosuvastatin is a substrate for both transporters. Silymarin inhibited both OATP1B1- and BCRP-mediated rosuvastatin transport in vitro (K i 0.93 μM and 97 μM, respectively). However, no significant changes in AUC, half-life, V d/F, or Cl/F of rosuvastatin were observed in human subjects following pretreatment with silymarin.

Conclusions

Silymarin does not appear to affect rosuvastatin pharmacokinetics in vivo, suggesting that silymarin, administered according to a recommended supplementation regimen, is not a potent modulator of OATP1B1 or BCRP in vivo.

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Abbreviations

BCRP:

breast cancer resistance protein

DHEAS:

dehydroepiandrosterone 3-sulfate

LC-MS/MS:

liquid chromatography-tandem mass spectrometry

MRP1:

multidrug resistance-associated protein 1

OATP1B1:

organic anion transporting polypeptide 1B1

P-gp:

P-glycoprotein

SNP:

single nucleotide polymorphisms

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Acknowledgment

We thank Mi-Gyung Go for her excellent technical assistance.

This work was supported by a grant from the Medical Research Center program (R13-2007-023-00000-0), KOSEF, Ministry of Science and Technology, Korea, and a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Korea (A030001, A040155).

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Authors and Affiliations

  1. Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, 633-165 Gaegum-Dong, Jin-Gu, Busan, 614-735, South Korea

    Jian Wei Deng, Ji-Hong Shon, Ho-Jung Shin, Soo-Jin Park, Chang-Woo Yeo, Hong-Hao Zhou, Im-Sook Song & Jae-Gook Shin

  2. Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, 614-735, South Korea

    Ji-Hong Shon, Chang-Woo Yeo & Jae-Gook Shin

  3. Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, 410078, People’s Republic of China

    Jian Wei Deng & Hong-Hao Zhou

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  1. Jian Wei Deng
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Correspondence to Im-Sook Song or Jae-Gook Shin.

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Deng, J.W., Shon, JH., Shin, HJ. et al. Effect of Silymarin Supplement on the Pharmacokinetics of Rosuvastatin. Pharm Res 25, 1807–1814 (2008). https://doi.org/10.1007/s11095-007-9492-0

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  • DOI: https://doi.org/10.1007/s11095-007-9492-0

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