The influence of ABCB1 polymorphism C3435T on the pharmacokinetics of silibinin

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Abstract

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 whetherABCB1C3435T polymorphism influenced the pharmacokinetics of silibinin contained in silymarin capsules.

Methods:

Twenty-three healthy volunteers (10ABCB1CC, 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) (withP= 0·0007 andP= 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 byABCB1 C3435Tpolymorphism. 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.

ABCB1 C3435T polymorphism affect the pharmacokinetics of silybinin after oral administration.

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