Relative Bioavailability of Silybin A and Silybin B From 2 Multiconstituent Dietary Supplement Formulations Containing Milk Thistle Extract: A Single-dose Study

Abstract

Purpose: The purpose of this study was to compare the bioavailability between 2 milk thistle-containing dietary supplements, Product B and IsaGenesis, in healthy volunteers.

Methods: Bioavailability between Product B, originally formulated as a powdered capsule, and IsaGenesis, reformulated as a soft gel, were compared by measuring silybin A and silybin B as surrogate pharmacokinetic markers for differences in absorption and bioavailability. For this randomized, open-label, crossover pharmacokinetic study, 12 healthy volunteers consumed a single-dose serving of each supplement separated by at least a 7-day washout period. Serial blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and analyzed via LC-MS/MS.

Findings: Rapid absorption and elimination of silybin A and silybin B have been observed after oral administration of both Product B and IsaGenesis. However, the absorption rate and extent, as indicated by mean the C_max and mean plasma AUC, were significantly higher for the IsaGenesis soft gel formulation. The dose-corrected mean C_max was 365% and 450% greater for silybin A and B, respectively, relative to powdered Product B. The time to T_max was reached, on average, at least 1 hour earlier with IsaGenesis relative to Product B for both silybin A and silybin B.

Implications: The IsaGenesis soft gel formulation provided substantially greater absorption and bioavailability of silybin A and silybin B relative to the powdered Product B supplement. ClinicalTrials.gov Identifier: NCT02529605.

Keywords: absorption; formulation; milk thistle; pharmacokinetic properties; silybin.

Figure 1

Structures of Silybin A and Silybin B.

Figure 2

Mean plasma concentrations of silybin A versus time profiles after oral administration of single doses of Product B and IsaGenesis in 12 healthy volunteers.

Figure 3

Mean plasma concentrations of silybin B versus time profiles after oral administration of single doses of Product B and IsaGenesis in 12 healthy volunteers.

Figure 4

Mean plasma concentrations of silybin (A+B) versus time profiles after oral administration of single doses of Product B and IsaGenesis in 12 healthy volunteers.

Figure 5

Box plots of AUC_last/Dose (h*ng/ml/mg) of Silybin A.

Figure 6

Box plots of C_max/Dose (ng/ml/mg) of Silybin A.

Figure 7

Box plots of AUC_last/Dose (h*ng/ml/mg) of Silybin B.

Figure 8

Box plots of Cmax/Dose (ng/ml/mg) of Silybin B.