论文部分内容阅读
传统中药钩藤中主要的活性成分为钩藤碱。现代中药药理研究表明,钩藤碱主要作用于心血管系统和中枢神经系统。关于钩藤碱在食草动物兔体内的药代动力学特征还未见报道,由于临床前不同种属动物体内药代动力学研究对设计人体的药代学参数有重要意义,所以本文采用对兔体内血药浓度的测定来研究钩藤碱的药代动力学,并建立了快速灵敏的UPLC-MS/MS分析方法来测定血浆药物浓度。结果表明,钩藤碱在0.01–10.24μg/m L的浓度范围内呈线性,日内、日间变异系数均小于8.0%,相对回收率在94.17%–103.32%之间,基质效应影响小。给兔灌胃三个剂量(20、40、80 mg/kg)的钩藤碱后,血浆中的消除相t1/2分别为1.19 h、1.49 h和1.37 h,在20–80 mg/kg的剂量范围内曲线下的面积AUC∞和达峰浓度Cmax与给药剂量的线性呈正相关。所以本实验不仅可用于钩藤碱体内药代动力学研究,也为设计和优化临床研究给药方案提供有关依据和参考。
Traditional Chinese medicine Uncaria in the main active ingredient is rhynchophylline. Modern Chinese pharmacological studies have shown that rhynchophylline main role in the cardiovascular system and the central nervous system. Pharmacokinetic characteristics of rhynchophylline in herbivore rabbits have not been reported yet. Since pharmacokinetic studies in different species of animals before preclinical studies are of great significance for designing pharmacokinetic parameters of human body, The pharmacokinetics of rhynchophylline was studied by measuring the plasma concentration in rabbit and the fast and sensitive UPLC-MS / MS method was established to determine the concentration of plasma drug. The results showed that the concentration of rhynchophylline was linear in the range of 0.01-10.24μg / m L, the intra-day and inter-day coefficient of variation were less than 8.0%, the relative recoveries were between 94.17% and 103.32%, and the effect of matrix was little. After administration of three doses of rhynchophylline (20,40,80 mg / kg) to rabbits, the elimination phase t1 / 2 in plasma was 1.19 h, 1.49 h and 1.37 h, respectively, at 20-80 mg / kg The area under the curve AUC∞ and the peak concentration Cmax in the dose range were positively correlated with the linearity of the dose administered. Therefore, this experiment can not only be used for in vivo pharmacokinetic study of rhynchophylline, but also provide relevant basis and reference for the design and optimization of clinical research dosing regimen.