Tags

Type your tag names separated by a space and hit enter

Effect of silymarin supplement on the pharmacokinetics of rosuvastatin.
Pharm Res. 2008 Aug; 25(8):1807-14.PR

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 microM and 97 microM, respectively). However, no significant changes in AUC, half-life, Vd/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.

Authors+Show Affiliations

Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, 633-165 Gaegum-Dong, Jin-Gu, Busan, 614-735, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18236139

Citation

Deng, Jian Wei, et al. "Effect of Silymarin Supplement On the Pharmacokinetics of Rosuvastatin." Pharmaceutical Research, vol. 25, no. 8, 2008, pp. 1807-14.
Deng JW, Shon JH, Shin HJ, et al. Effect of silymarin supplement on the pharmacokinetics of rosuvastatin. Pharm Res. 2008;25(8):1807-14.
Deng, J. W., Shon, J. H., Shin, H. J., Park, S. J., Yeo, C. W., Zhou, H. H., Song, I. S., & Shin, J. G. (2008). Effect of silymarin supplement on the pharmacokinetics of rosuvastatin. Pharmaceutical Research, 25(8), 1807-14. https://doi.org/10.1007/s11095-007-9492-0
Deng JW, et al. Effect of Silymarin Supplement On the Pharmacokinetics of Rosuvastatin. Pharm Res. 2008;25(8):1807-14. PubMed PMID: 18236139.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of silymarin supplement on the pharmacokinetics of rosuvastatin. AU - Deng,Jian Wei, AU - Shon,Ji-Hong, AU - Shin,Ho-Jung, AU - Park,Soo-Jin, AU - Yeo,Chang-Woo, AU - Zhou,Hong-Hao, AU - Song,Im-Sook, AU - Shin,Jae-Gook, Y1 - 2008/01/31/ PY - 2007/08/27/received PY - 2007/10/29/accepted PY - 2008/2/1/pubmed PY - 2008/10/4/medline PY - 2008/2/1/entrez SP - 1807 EP - 14 JF - Pharmaceutical research JO - Pharm. Res. VL - 25 IS - 8 N2 - 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 microM and 97 microM, respectively). However, no significant changes in AUC, half-life, Vd/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. SN - 0724-8741 UR - https://www.unboundmedicine.com/medline/citation/18236139/Effect_of_silymarin_supplement_on_the_pharmacokinetics_of_rosuvastatin_ L2 - https://doi.org/10.1007/s11095-007-9492-0 DB - PRIME DP - Unbound Medicine ER -