Bioavailability augmentation of silymarin using natural bioenhancers: An in vivo pharmacokinetic study

Abstract Pharmacokinetic studies were carried out in male and female rats to quantify silymarin as silybin (A+B) after the oral administration of various silymarin formulations combined with three bioenhancers, namely, lysergol, piperine, and fulvic acid, and compared with plain silymarin formulation (control). A non-compartmental analysis, model independent analysis, was utilized, and various pharmacokinetic parameters (C max, T max, and AUC 0-t) were calculated individually for each treatment group, and the values were expressed as mean ± SEM (n = 6). Plasma samples obtained from the rats were analyzed for the concentration of silymarin through a validated RP-HPLC method and on the basis of data generated from the pharmacokinetic studies. Results indicated that the bioenhancers augmented pharmacokinetic parameters and bioavailability increased 2.4-14.5-fold in all the formulations compared with the control. The current work envisages the development of an industrially viable product that can be further subjected to clinical trials and scientifically supports the development of silymarin as a contemporary therapeutic agent with enhanced bioavailability and medicinal values.

摘要：本研究针对雌雄大鼠开展药代动力学研究，以水飞蓟宾（A+B）为定量指标，检测不同水飞蓟素制剂分别配伍三种生物增强剂（赖瑟醇、胡椒碱与富里酸）后的体内过程，并与空白水飞蓟素制剂（对照组）进行对照。本研究采用非房室分析（无模型分析）方法，对各给药组的多项药代动力学参数（C_max、T_max及AUC_0-t）分别进行计算，结果以平均值±标准误（n=6）表示。采用经过验证的反相高效液相色谱（RP-HPLC）法对大鼠血浆样本中的水飞蓟素浓度进行定量检测，并基于本药代动力学研究获得的实验数据开展分析。结果显示，相较于对照组，各制剂配伍生物增强剂后均可提升药代动力学参数，且生物利用度提升2.4~14.5倍。本研究旨在开发工业化生产可行的相关产品，可进一步开展临床试验，同时为水飞蓟素作为兼具更高生物利用度与药用价值的现代治疗药物的开发提供科学支撑。