摘要
目的 研究仙灵脾颗粒中主要成分在大鼠血浆内的药代动力学及整合药代动力学行为,以探讨其长期临床用药时间间隔的合理性.方法 取12只雄性SD大鼠,随机分组后给予给药组大鼠仙灵脾颗粒8.1g/(kg·d),连续给药7 d后,于给药前及给药后0.25、0.5、1、2、3、4、6、8、12h大鼠眼眶后静脉丛取血0.5 mL,通过UPLC-QQQ-MS技术测定大鼠血浆内不同时间点淫羊藿属苷A、朝藿定A、朝藿定B、朝藿定C、淫羊藿苷、宝藿苷Ⅱ、淫羊藿次苷Ⅰ及宝藿苷Ⅰ的血药浓度,并分别赋予8个成分抗骨质疏松药效权重系数进行整合,采用DAS 3.2.8软件计算血浆药代动力学参数并得到血药浓度-时间曲线.结果 大鼠连续多次给药后,8种成分在血浆内的药代动力学参数:tmax均为0.5 h,Cmax为1.36～48.76 ng·mL-1,t1/2 为 8.50～81.40 h,AUC0～t 为 14.52～138.19 ng·mL-1·h,MRT0～t为3.27～5.96 h;扣除0 h时间点血药浓度后所有成分在血浆内的药代动力学参数:tmax均为0.5 h,Cmax为 0.18～40.37 ng·mL-1,t1/2 为 1.00～3.00 h,AUC0～t为 0.40～37.49 ng·mL-1·h,MRT0～t为1.51～4.41 h;8种成分赋予抗骨质疏松药效权重后,整合药代动力学参数:tmax=0.5 h、t1/2=(1.92±0.42)h.结论 通过对仙灵脾颗粒血浆内药代动力学进行研究,阐明了其临床给药时间间隔的合理性,同时为仙灵脾颗粒抗骨质疏松药效物质基础研究提供依据及参考.
Abstract
Objective To determine the pharmacokinetics and integrative pharmacokinetic behaviours of the main components of Xianlingpi granules in rat plasma,and the rational of the time interval for long-term clinical dosing of Xianlingpi granules.Methods Totally 12 male SD rats were divided into two groups randomly(a treatment group and a blank group),and the rats in the treatment group were given Xianlingpi granules at 8.1 g/(kg·d).After 7 days of continuous intragastric administration,0.5 mL blood was collected from the retor-orbital venous plexus of the rats before the dose and at 0.25,0.5,1,2,3,4,6,8 and 12 h after the administration.The concentration of epimedoside A,epimedin A,epimedin B,epimedin C,icariin,baohuoside Ⅱ,icariside Ⅰ,and baohuoside Ⅰ in the rat plasma at different time points were determined with UPLC-QQQ-MS,and intergrated weight coefficients were assigned for the anti-osteoporosis efficacy of 8 components respectively.DAS 3.2.8 software was used to calculate the pharmacokinetic parameters of the plasma and obtain the plasma concentration-time profiles.Results After multiple consecutive administrations in the rats,the intraplasma pharmacokinetic parameters of the 8 components showed tmax of 0.5 h,Cmax of 1.36～48.76 ng·mL-1,t1/2 of 8.50～81.40 h,anAUC0～t of 14.52～138.19 ng·mL-1·h,and MRT0～t of 3.27～5.96 h.After deducting the concentration of plasma components at the time point of 0 h,the tmax of all components in the plasma was 0.5 h,Cmax was 0.18～40.37 ng·mL-1t1/2 was 1.00～3.00 h,AUC0～t was 0.40～37.49 ng·mL-1·h and MRT0～t was 1.51～4.41 h.After assigning weight coefficients to the anti-osteoporosis efficacy of the 8 components,the pharmacokinetic parameters for component integration such as tmax was 0.5 h,and t1/2 was(1.92±0.42)h.Conclusion By studying the pharmacokinetic in plasma,the rationality of the clinical administration time interval of Xianlingpi granules is elucidated,providing reference for the material basis for the anti-osteoporosis efficacy of Xianlingpi granules.
基金项目
辽宁省科技厅揭榜挂帅项目(2021JH1/10400058)
NETL
NSTL
万方数据