Drug Interaction Study: Silymarin does not adversely interact with rosuvastatin (Crestor). - GreenMedInfo Summary
Effect of silymarin supplement on the pharmacokinetics of rosuvastatin.
Pharm Res. 2008 Aug;25(8):1807-14. Epub 2008 Jan 31. PMID: 18236139
Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, 633-165 Gaegum-Dong, Jin-Gu, Busan, 614-735, South Korea.
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.