Effect of Silymarin Supplement on the Pharmacokinetics of Rosuvastatin

• Published in: Pharmaceutical research 2008-08, Vol.25 (8), p.1807-1814
• Main Authors: Deng, Jian Wei, Shon, Ji-Hong, Shin, Ho-Jung, Park, Soo-Jin, Yeo, Chang-Woo, Zhou, Hong-Hao, Song, Im-Sook, Shin, Jae-Gook
• Format: Article
• Language: English
• Subjects: Adult; Algorithms; Antioxidants - pharmacology; Area Under Curve; ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters - metabolism; Biochemistry; Biological and medical sciences; Biological Transport, Active - drug effects; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cell Line, Tumor; Cellular biology; Cross-Over Studies; Dietary Supplements - adverse effects; Drug Interactions; Female; Fluorobenzenes - pharmacokinetics; General pharmacology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; Kinetics; Male; Medical Law; Medical sciences; Neoplasm Proteins - metabolism; Organic Anion Transporters - metabolism; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Pyrimidines - pharmacokinetics; Research Paper; Rosuvastatin Calcium; Silymarin - pharmacology; Solute Carrier Organic Anion Transporter Family Member 1b1; Statins; Sulfonamides - pharmacokinetics
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-007-9492-0

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 .