title: Effect of silymarin supplement on the pharmacokinetics of rosuvastatin.
abstract: OBJECTIVE
  To evaluate the effect of silymarin on the pharmacokinetics of rosuvastatin in systems overexpressing OATP1B1 or BCRP transporters and in healthy subjects.
  
  
  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.affiliation: Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, 633-165 Gaegum-Dong, Jin-Gu, Busan, 614-735, South Korea.
authors.forename: Jian Wei
authors.initials: JW
authors.lastname: Deng
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Shon
authors.forename: Ho-Jung
authors.initials: HJ
authors.lastname: Shin
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Yeo
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.forename: Im-Sook
authors.initials: IS
authors.lastname: Song
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000465:Algorithms; D000975:Antioxidants / Q000494:pharmacology*; D019540:Area Under Curve; D001693:Biological Transport, Active / Q000187:drug effects; D045744:Cell Line, Tumor; D018592:Cross-Over Studies; D019587:Dietary Supplements / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D005464:Fluorobenzenes / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D011743:Pyrimidines / Q000493:pharmacokinetics*; D000068718:Rosuvastatin Calcium; D012838:Silymarin / Q000494:pharmacology*; D013449:Sulfonamides / Q000493:pharmacokinetics*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000975:Antioxidants; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; D011743:Pyrimidines; C503999:SLCO1B1 protein, human; D012838:Silymarin; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium