title: The influence of ABCB1 polymorphism C3435T on the pharmacokinetics of silibinin.
abstract: OBJECTIVE
  Silibinin (Silybin), a major constituent of the milk thistle, is commonly used to treat chronic liver disease in some countries. It has been reported to inhibit the transport activity of ABCB1. This study was carried out to determine whether ABCB1 C3435T polymorphism influenced the pharmacokinetics of silibinin contained in silymarin capsules.
  
  
  METHODS
  Twenty-three healthy volunteers (10 ABCB1 CC, 8 CT and 5 TT genotypes) were enrolled in this clinical trial. Each volunteer was given a single dose of 140 mg Silymarin Capsule. Blood samples were then collected up to 12 h. HPLC-MS/MS was used to detect serial blood concentration of silybin.
  
  
  CONCLUSIONS
  The peak plasma concentration (Cmax) in subjects of CC (144·8 ± 60·1 ng/mL) and CT (129·3 ± 50·3 ng/mL) genotypes were 2-fold higher than in subjects of TT genotype (60·1 ± 18·3 ng/mL) (with P = 0·0007 and P = 0·0115 respectively). The area under the concentration-time curve (AUC) extrapolated to infinity [AUC(0-∞)] of CC carriers (347·1 ± 133·8 ng/mL h) was significantly higher than that of TT carriers (228·3 ± 52·9 ng/mL h) (P = 0·0115).
  
  
  CONCLUSIONS
  The pharmacokinetics of silibinin was significantly influenced by ABCB1 C3435T polymorphism. Dosage adjustment may be necessary for subjects of different genotypes to ensure comparative exposures. A dose-ranging clinical trial should be undertaken to determine whether the observed differences are clinically significant.
authors.affiliation: Department of Clinical Pharmacology, Xiang Ya Hospital of Central South University, Chang Sha, China.
authors.forename: Z R
authors.initials: ZR
authors.lastname: Tan
authors.affiliation: Department of Clinical Pharmacology, Xiang Ya Hospital of Central South University, Chang Sha, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiang Ya Hospital of Central South University, Chang Sha, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Xiang Ya Hospital of Central South University, Chang Sha, China.
authors.forename: W H
authors.initials: WH
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacology, Xiang Ya Hospital of Central South University, Chang Sha, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacology, Xiang Ya Hospital of Central South University, Chang Sha, China.
authors.forename: Y C
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Xiang Ya Hospital of Central South University, Chang Sha, China.|Institute of Clinical Pharmacology, Central South University, Chang Sha, China.
authors.forename: L S
authors.initials: LS
authors.lastname: Wang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D019540:Area Under Curve; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D000077385:Silybin; D012838:Silymarin / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D012838:Silymarin; D000077385:Silybin
keywords: P-glycoprotein; pharmacogenetics; pharmacokinetic; silibin