Peng Yunru, Ding Yongfang
Department of Pharmacology and Toxicology, Jiangsu Provincial Institute of Traditional Chinese Medicine, 100 Shizi Street, Nanjing 210028, China.
Molecules. 2015 Mar 5;20(3):4225-37. doi: 10.3390/molecules20034225.
Caudatin is a potential antitumor agent isolated from the traditional Chinese medicine "baishouwu", which was the root tuber of Cynanchum auriculatum Royle ex Wight. In our previous studies, caudatin showed selectivity on human hepatoma cell line SMMC7721 among several different tumor cell lines, and further in vivo tests validated the inhibitory action of caudatin against hepatic cancer using an H22 solid tumor model in mice, but to our knowledge, the biopharmaceutical properties of caudatin are largely unknown. In this study, a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of caudatin in rat plasma and tissues, which kept the run time to detect one sample within 4 min, was developed and validated. Pharmacokinetics and tissue distribution studies of caudatin in conventional rats and hepatocellular carcinoma (HCC) model rats were then conducted for the first time. Statistically significant differences were observed between conventional rats and diethylnitrosamine (DEN)-induced HCC rats with respect to pharmacokinetic parameters, including maximum concentration (Cmax), time to reach Cmax (Tmax), half-life (t1/2), area under the concentration-time curve (AUC0-t, AUC0-∞), mean residence time (MRT0-t and MRT0-∞), and oral clearance (CL/F). Increased exposures of caudatin were found in the plasma and livers of HCC model rats, which would be helpful for a better understanding of pharmacological effect of caudatin in treating HCC disease.
考达定是从传统中药“白首乌”中分离出的一种潜在抗肿瘤药物，白首乌为耳叶牛皮消的块根。在我们之前的研究中，考达定在几种不同的肿瘤细胞系中对人肝癌细胞系SMMC7721表现出选择性，并且进一步的体内试验使用小鼠H22实体瘤模型验证了考达定对肝癌的抑制作用，但据我们所知，考达定的生物药剂学性质在很大程度上尚不清楚。在本研究中，开发并验证了一种简单、快速且灵敏的超高效液相色谱-串联质谱（UPLC-MS/MS）方法，用于测定大鼠血浆和组织中的考达定，该方法检测一个样品的运行时间保持在4分钟以内。随后首次对考达定在正常大鼠和肝细胞癌（HCC）模型大鼠中的药代动力学和组织分布进行了研究。在正常大鼠和二乙基亚硝胺（DEN）诱导的HCC大鼠之间，观察到药代动力学参数存在统计学显著差异，包括最大浓度（Cmax）、达到Cmax的时间（Tmax）、半衰期（t1/2）、浓度-时间曲线下面积（AUC0-t、AUC0-∞）、平均驻留时间（MRT0-t和MRT0-∞）以及口服清除率（CL/F）。在HCC模型大鼠的血浆和肝脏中发现考达定的暴露量增加这将有助于更好地理解考达定治疗HCC疾病的药理作用。
