The influence of ABCB1 polymorphism C3435T on the pharmacokinetics of silibinin

Summary What is known and 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. Results and discussion 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). What is new and conclusion 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.