Méndez-Sánchez Nahum, Dibildox-Martinez Miguel, Sosa-Noguera Jahir, Sánchez-Medal Ramón, Flores-Murrieta Francisco J
Liver Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150, Col. Toriello Guerra, 14050, Mexico City, Mexico.
Italmex Pharma, 04850, Mexico City, Mexico.
BMC Pharmacol Toxicol. 2019 Jan 11;20(1):5. doi: 10.1186/s40360-018-0280-8.
Fibrosis is a response to chronic liver disease that results in excessive accumulation of extracellular matrix proteins and formation of scar tissue. Fibrosis represents a clinical challenge of worldwide significance. Several studies have demonstrated that many natural products and herbal medicines have activity against liver fibrosis, and extracts of milk thistle such as silymarin and silybin are the natural compounds most commonly prescribed for liver diseases. Therefore, we sought to assess and compare the pharmacokinetic properties and bioavailability of silybin-phosphatidylcholine complex in oily-medium soft-gel capsules and conventional silymarin tablets in healthy Mexican volunteers.
We enrolled 23 healthy volunteers to participate in a prospective, balanced, blind, single-dose, two-way crossover study with a one-week washout period. Fasting participants received either 45 mg silybin-phosphatidylcholine complex or 70 mg silymarin to assess which formulation provided better bioavailability of silybin. Plasma was obtained and analysed for silybin concentration using a validated ultra-performance liquid chromatography-tandem mass spectroscopy method. Pharmacokinetic parameters were obtained by non-compartmental analysis and values were compared by analysis of variance for a crossover design. Ratios of maximum plasma drug concentration and area under the curve (AUC) were obtained and 90% confidence intervals were calculated.
The 23 healthy subjects (11 women, 12 men) who participated in the study were aged 22-31 years old (average: 28), average weight 64.8 kg, height 1.65 m and body mass index 23.5 kg/m. Plasma levels of silybin were higher after the administration of silybin-phosphatidylcholine complex capsules compared with that after conventional silymarin tablets (P < 0.0001).
The silybin-phosphatidylcholine complex in oily-medium soft-gel capsules seems to provide superior bioavailability. However, clinical studies must be performed to demonstrate its clinical relevance in the treatment of liver diseases.
NCT03440164 ; registered on November 11, 2016.
肝纤维化是对慢性肝病的一种反应，会导致细胞外基质蛋白过度积累和瘢痕组织形成。肝纤维化是一个具有全球意义的临床挑战。多项研究表明，许多天然产物和草药对肝纤维化具有活性，水飞蓟提取物如水飞蓟素和水飞蓟宾是最常用于治疗肝病的天然化合物。因此，我们试图评估和比较健康墨西哥志愿者中，水飞蓟宾 - 磷脂酰胆碱复合物油媒软胶囊和传统水飞蓟素片的药代动力学特性和生物利用度。
我们招募了23名健康志愿者，参与一项前瞻性、均衡、盲法、单剂量、双向交叉研究，洗脱期为一周。空腹参与者分别接受45毫克水飞蓟宾 - 磷脂酰胆碱复合物或70毫克水飞蓟素，以评估哪种制剂能提供更好的水飞蓟宾生物利用度。采集血浆，使用经过验证的超高效液相色谱 - 串联质谱法分析水飞蓟宾浓度。通过非房室分析获得药代动力学参数，并通过交叉设计的方差分析比较数值。获得最大血浆药物浓度和曲线下面积（AUC）的比值，并计算90%置信区间。
参与研究的23名健康受试者（11名女性，12名男性）年龄在22 - 31岁（平均：28岁），平均体重64.8千克，身高1.65米，体重指数23.5千克/平方米。与传统水飞蓟素片相比，服用水飞蓟宾 - 磷脂酰胆碱复合物胶囊后血浆中的水飞蓟宾水平更高（P < 0.0001）。
油媒软胶囊中的水飞蓟宾 - 磷脂酰胆碱复合物似乎具有更高的生物利用度。然而，必须进行临床研究以证明其在肝病治疗中的临床相关性。
NCT03440164；于2016年11月11日注册。
