Skottová N, SVagera Z, Vecera R, Urbánek K, Jegorov A, Simánek V
Institute of Pharmacology, Medical Faculty, Palacký University, Olomouc, Czech Republic.
Pharmacol Res. 2001 Sep;44(3):247-53. doi: 10.1006/phrs.2001.0854.
The very low bioavailability of silibinin (silybin, SB), the main antioxidant flavonolignan of silymarin from Silybum marianum L. (Asteraceae), requires sensitive methods to study the modulation of silibinin bioavailability. To evaluate the potential for use of radiolabeled silibinin, two silibinin derivatives, separated by HPLC after iodination ((125)I-SB(1) and (125)I-SB(2)) and their complexes 1 : 1 with phosphatidylcholine ((125)I-SPC(1) and (125)I-SPC(2)) were administered concurrently with a single intragastric dose of 5.0 mg or 50 mg of unlabeled silibinin (alone or as a constituent of the complex) per kg of body weight in a comparative study of bioavailability in the rat. Pharmacokinetic parameters as well as organ uptake of (125)I-SB(1)-derived radioactivity showed a dose-response pattern. The parameters of bioavailability after (125)I-SPC(1) intake were not influenced by unlabeled silibinin (complexed with phosphatidylcholine), since maximal levels were achieved by the lower dose of unlabeled compound. The superior bioavailability of (125)I-SPC(1) was obvious at the lower dose of unlabeled compound as elevated AUC and RA(max) (maximal percentage of administered radioactivity), and increased radioactivity in liver, kidney, spleen and heart. An absence of these characteristics with (125)I-SB(2) and (125)I-SPC(2) suggests the use of(125)I-SB(1) for studies of modulation of its bioavailability in vivo in rat.
水飞蓟宾（水飞蓟素，SB）是水飞蓟（菊科）中主要的抗氧化黄酮木脂素，其生物利用度极低，因此需要灵敏的方法来研究水飞蓟宾生物利用度的调节。为评估放射性标记水飞蓟宾的应用潜力，在一项大鼠生物利用度对比研究中，将两种经碘化后通过高效液相色谱分离的水飞蓟宾衍生物（(125)I-SB(1)和(125)I-SB(2)）及其与磷脂酰胆碱1:1形成的复合物（(125)I-SPC(1)和(125)I-SPC(2)）与每千克体重5.0毫克或50毫克未标记的水飞蓟宾（单独或作为复合物的成分）单次灌胃给药。(125)I-SB(1)衍生放射性的药代动力学参数以及器官摄取呈现剂量反应模式。(125)I-SPC(1)摄入后的生物利用度参数不受未标记水飞蓟宾（与磷脂酰胆碱复合）的影响，因为较低剂量的未标记化合物即可达到最高水平。在较低剂量的未标记化合物情况下，(125)I-SPC(1)具有更高的生物利用度，表现为AUC和RA(max)（给药放射性的最大百分比）升高，以及肝脏、肾脏、脾脏和心脏中的放射性增加。(125)I-SB(2)和(125)I-SPC(2)缺乏这些特征，这表明(125)I-SB(1)可用于大鼠体内其生物利用度调节的研究。
