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汉防己甲素是从中药汉防己的块根中提取的一种双苄基异喹啉类生物碱,能够逆转肿瘤细胞多药耐药、诱导细胞凋亡,临床上用于治疗恶性肿瘤。本研究的目的是评价汉防己甲素在大鼠体内血液药动学、组织分布和排泄过程。大鼠通过静脉给予汉防己甲素注射液(10.00 mg/kg),应用高效液相色谱法测定血浆和各组织中的药物浓度,利用药动学软件DAS 2.0对实验数据进行计算分析。实验结果表明,汉防己甲素的血浆蛋白结合率为68.7%,属于较高蛋白结合率药物;组织分布药量由高到低依次是肺>心>肝>肾>脾;肾脏排泄是汉防己甲素主要的排泄途径,其通过尿液、胆汁和粪便排泄占给药剂量的13.09%。汉防己甲素在肝脏的AUC0–∞是血浆中AUC0–∞的20倍,表明其对肝脏有较高的亲和力;在所有的组织中肝脏CL是最低的,表明汉防己甲素清除缓慢,可能导致蓄积。因此,临床上长期药时,需要调整肝肾功能损伤病人的用药剂量,必要时进行治疗药物监测。
Tetrandrine is a kind of double-benzyl isoquinoline alkaloid extracted from the root of Chinese Han Fang Ji, which can reverse the multidrug resistance of tumor cells, induce apoptosis and is used clinically to treat malignant tumors. The purpose of this study was to evaluate the pharmacokinetics, tissue distribution and excretion of tetrandrine in rats. Rats were intravenously administered with tetrandrine injection (10.00 mg / kg), and the plasma and tissue concentrations were determined by HPLC. The experimental data were calculated and analyzed by using the pharmacokinetics software DAS 2.0. The experimental results showed that the plasma protein binding rate of tetrandrine was 68.7%, belonging to the drug with higher protein binding rate; the tissue drug distribution distribution was lung> heart> liver> kidney> spleen from high to low; A main excretion pathway, which through the urine, bile and excretion accounted for 13.09% of the dose. Tetracycline AUC0-∞ in the liver is 20 times higher than AUC0-∞ in plasma, indicating that it has a high affinity for the liver; liver CL is the lowest in all tissues, indicating a slow clearance of tetrandrine that may Lead to accumulation. Therefore, clinically long-term drugs, need to adjust the dosage of patients with liver and kidney dysfunction, if necessary, for the treatment of drug monitoring.