Abstracts

1. Zhenwu Tang (ZWT) is a traditional Chinese medicine that is primarily composed of Radix Aconiti Lateralis Praeparata (FZ) and diterpenoid alkaloids are believed to be the pharmacologically active compounds of ZWT. In this study, the pharmacokinetic profiles of hypaconitine, mesaconitine, aconitine, benzoylmesaconitine, benzoylaconitine, and benzoylhypacoitine were assessed in rats following intragastric ZWT administration. Furthermore, differences in the pharmacokinetic profiles of these six alkaloids were assessed as a function of rat sex and the administration of ZWT or FZ extracts to these animals. Plasma levels of these alkaloids were quantified via HPLC-MS/MS.

2. Significant differences in key pharmacokinetic parameters were observed when comparing rats administered FZ or ZWT. Relative to FZ extract treatment, ZWT administration was associated with C_max and AUC_0-∞ values of benzoylmesaconitine that were about 3.5 and 5.5 times higher. Considerable variations in hypaconitine pharmacokinetic parameters were also revealed between female and male rats. The C_max and AUC_0-∞ of hypaconitine were about 2.5 and 2.7 fold elevated in female rats in comparison with male rats.

3. These results suggested that the other compounds within ZWT can enhance the absorption of benzoylmesaconitine, while hypaconitine exhibits higher bioavailability in female rats, as compared with male rats.

摘要

1. 真武堂（ZWT）是一种主要由乌头（FZ）和二萜生物碱组成的中药，被认为是ZWT的药理活性化合物。在这项研究中，评估了胃内ZWT给药后大鼠中的高烟碱，中速肉碱，乌头碱，苯甲酰基美考尼汀，苯甲酰肾上腺素和苯甲酰基高糖碱的药代动力学特征。此外，根据大鼠性别以及对这些动物施用ZWT或FZ提取物，评估了这6种生物碱在药代动力学方面的差异。这些生物碱的血浆水平通过HPLC-MS / MS定量。

2. 当比较施用FZ或ZWT的大鼠时，观察到关键药代动力学参数的显着差异。相对于FZ提取物处理，ZWT施用与苯甲酰_基美舒尼汀的C _max和AUC0 _-∞值分别高约3.5倍和5.5倍。在雌性和雄性大鼠之间还发现了猪笼草碱药代动力学参数的显着变化。与雄性大鼠相比，雌性大鼠的猪笼草碱的C _max和AUC0 _-∞分别升高了2.5倍和2.7倍。

3. 这些结果表明，与雄性大鼠相比，ZWT中的其他化合物可以增强苯甲酰基美舒尼汀的吸收，而猪笼草碱在雌性大鼠中显示出更高的生物利用度。