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目的:以群体药物动力学原理分析复方冠心Ⅱ不同组成条件对主要组分芍药苷及阿魏酸体内过程的影响。方法:将大鼠随机分组后分别静脉注射芍药苷(PPE)或阿魏酸(FA)提取物水溶液、灌胃给予PPE或FA水溶液及不同组成的水煎液,HPLC法测定血浆中芍药苷和阿魏酸浓度,以非线性混合效应模型(NONMEM)法分别对芍药苷和阿魏酸的血药浓度数据进行群体药物动力学解析。结果:芍药苷的体内药物动力学过程可用吸收相包含一级降解过程的二室口服吸收模型进行表述,参数CL1、V1、CL2、V2、Ka0和Ka1分别为0.509 L/h, 0.104 L,0.113 L/h,0.123 L,0.135/h及0.0135/h;阿魏酸的体内过程可用二室口服吸收模型表述,参数CL1、V1、CL2、V2,、Ka及F分别为0.295 L/h、0.025 L、0.0331 L/h、0.0518 L、0.110/h及0.40。模型化中对个体间差异进行了估计,并以给药组方因素(DF)作为固定效应对参数进行了校正。结论:群体药物动力学方法可以用于分析中药复方冠心Ⅱ中组方变化对其中指标成分的体内吸收和分布产生的影响,较以往的方法有一定的优越性。
OBJECTIVE: To analyze the effect of different compositional conditions of compound Guanxin II on the internal processes of paeoniflorin and ferulic acid in the main component by the principle of population pharmacokinetics. METHODS: Rats were randomly divided into groups and intravenously injected with an aqueous solution of paeoniflorin (PPE) or ferulic acid (FA) extract, intragastrically administered PPE or FA solution, and decoctions of different compositions. HPLC method was used to determine plasma paeoniflorin and The concentration of ferulic acid was determined by non-linear mixed effects (NONMEM) method. The pharmacokinetics of peonidin and ferulic acid were analyzed by population pharmacokinetics. RESULTS: The in vivo pharmacokinetics of paeoniflorin can be described by a two-chamber oral absorption model in which the absorption phase includes a first-order degradation process. The parameters CL1, V1, CL2, V2, Ka0, and Ka1 are 0.509 L/h, 0.104 L, and 0.113, respectively. L/h, 0.123 L, 0.135/h, and 0.0135/h; the in vivo process of ferulic acid can be described by a two-chamber oral absorption model with parameters CL1, V1, CL2, V2, Ka, and F of 0.295 L/h and 0.025, respectively. L, 0.0331 L/h, 0.0518 L, 0.110/h, and 0.40. The differences between individuals were estimated in the modelling and the parameters were corrected using the dosing group factor (DF) as a fixed effect. Conclusion: The population pharmacokinetics method can be used to analyze the effects of changes in the Chinese herbal compound Guanxin II on the in vivo absorption and distribution of the index components, which has certain advantages over the previous methods.