Chang Chuck, Zhang Yiming, Kuo Yun Chai, Du Min, Roh Kyle, Gahler Roland, Ibi Afoke, Solnier Julia
ISURA, Burnaby, BC V3N4S9, Canada.
Factors Group R & D, Burnaby, BC V3N4S9, Canada.
Pharmaceutics. 2025 Jul 4;17(7):880. doi: 10.3390/pharmaceutics17070880.
Silymarin, a flavonoid complex, and the main bioactive component of milk thistle (), is known for its hepatoprotective properties but suffers from poor bioavailability due to its low solubility and extensive first-pass metabolism. This study aimed to evaluate the pharmacokinetics and tolerability of a novel micellar milk thistle formulation designed to enhance silymarin absorption, compared to an unformulated/standard milk thistle product, in a small-scale human bioavailability trial. In a randomized, double-blinded, crossover study, 16 healthy participants received a single dose of either the micellar formulation (LipoMicel Milk Thistle; LMM) or the standard formulation (STD) at a total daily dose of 130 mg silymarin. Blood concentrations were measured over 24 h, and key pharmacokinetic parameters-maximum plasma concentration (C), time to reach maximum concentration (T), and area under the curve (AUC)-were calculated. Tolerability and safety were assessed through adverse event monitoring during the study period. Results demonstrated a significant increase in bioavailability with the micellar formulation, with 18.9-fold higher C (95% CI: 1.9-30.7 ng/mL vs. 74.4-288.3 ng/mL; = 0.007) and 11.4-fold higher AUC (95% CI: 7.40-113.5 ng·h/mL vs. 178-612.5 ng·h/mL; = 0.015). T was 0.5 (95% CI: 0.5-4.0) hours for the micellar formulation versus 2.5 (95% CI: 0.5-8.0) hours for the standard product ( = 0.015) indicating faster absorption of LMM. The standard formulation exhibited a significantly longer mean residence time compared to the LMM formulation (95% CI: 4.4-7.5 h vs. 2.8-4.2 h; = 0.015). No adverse events or significant safety concerns were observed in either group. Compared to the standard, the micellar formulation showed superior pharmacokinetic outcomes, suggesting it may enhance silymarin's clinical efficacy in liver health.
水飞蓟素是一种类黄酮复合物，也是水飞蓟的主要生物活性成分，因其具有肝脏保护特性而闻名，但由于其低溶解度和广泛的首过代谢，生物利用度较差。本研究旨在通过一项小规模人体生物利用度试验，评估一种旨在提高水飞蓟素吸收的新型胶束水飞蓟制剂与未制剂化/标准水飞蓟产品相比的药代动力学和耐受性。在一项随机、双盲、交叉研究中，16名健康参与者接受了单剂量的胶束制剂（LipoMicel水飞蓟；LMM）或标准制剂（STD），水飞蓟素的每日总剂量为130mg。在24小时内测量血药浓度，并计算关键药代动力学参数——最大血浆浓度（Cmax）、达到最大浓度的时间（Tmax）和曲线下面积（AUC）。通过研究期间的不良事件监测评估耐受性和安全性。结果表明，胶束制剂的生物利用度显著提高，Cmax高18.9倍（95%CI：1.9 - 30.7 ng/mL对74.4 - 288.3 ng/mL；P = 0.007），AUC高11.4倍（95%CI：7.40 - 113.5 ng·h/mL对178 - 612.5 ng·h/mL；P = 0.015）。胶束制剂的Tmax为0.5（95%CI：0.5 - 4.0）小时，而标准产品为2.5（95%CI：0.5 - 8.0）小时（P = 0.015），表明LMM吸收更快。与LMM制剂相比，标准制剂的平均驻留时间显著更长（95%CI：4.4 - 7.5小时对2.8 - 4.2小时；P = 0.015）。两组均未观察到不良事件或重大安全问题。与标准制剂相比，胶束制剂显示出更好的药代动力学结果，表明它可能增强水飞蓟素对肝脏健康的临床疗效。
