刘润南, 唐昱, 刘平安, 刘文龙, 樊启猛, 陈思阳, 贺鹏, 李海英, 贺福元, 邓凯文. 用药物代谢速度代替浓度线性化Hill量效曲线的研究[J]. Digital Chinese Medicine, 2018, 1(3): 198-210.
引用本文: 刘润南, 唐昱, 刘平安, 刘文龙, 樊启猛, 陈思阳, 贺鹏, 李海英, 贺福元, 邓凯文. 用药物代谢速度代替浓度线性化Hill量效曲线的研究[J]. Digital Chinese Medicine, 2018, 1(3): 198-210.
LIU Run-Nan, TANG Yu, LIU Ping-An, LIU Wen-Long, FAN Qi-Meng, CHEN Si-Yang, HE Peng, LI Hai-Ying, HE Fu-Yuan, DENG Kai-Wen. Study of Linearization of Hill Dose-Effect Curve with Metabolic Velocity Instead of Drug Concentration[J]. Digital Chinese Medicine, 2018, 1(3): 198-210.
Citation: LIU Run-Nan, TANG Yu, LIU Ping-An, LIU Wen-Long, FAN Qi-Meng, CHEN Si-Yang, HE Peng, LI Hai-Ying, HE Fu-Yuan, DENG Kai-Wen. Study of Linearization of Hill Dose-Effect Curve with Metabolic Velocity Instead of Drug Concentration[J]. Digital Chinese Medicine, 2018, 1(3): 198-210.

用药物代谢速度代替浓度线性化Hill量效曲线的研究

Study of Linearization of Hill Dose-Effect Curve with Metabolic Velocity Instead of Drug Concentration

  • 摘要:
    目的从Hill量效与靶受体代谢动力学关系一致性角度探讨成分的速效关系,建立效应的线性化法。
    方法根据Hill量效方程与受体的Michaelis-Menten动力学关系,比其一致性,用多元微分方程组建立线性化的速效关系。并用乙酰胆碱、肾上腺素及两者混合液体外验证所创模型。
    结果建立了单成分及多成分,体内与体外的速效关系模型,发现采用饱和高浓度与线性低浓度实验可测算单成分与多成分的药效动力学参数,特别是能适宜中药复方多成分有效性的研究。乙酰胆碱的药效动力学参数k为2.675×10-3 s-1,ka为5.786×10-9 s-1,km为2.500×10-7 s-1,α为4.619×109张 s·m g-1,E0为13张(P < 0.01);肾上腺素的药效动力学参数k为1.415×10-3 s-1,ka为5.846×10-9 s-1,km为2.300×10-7 s-1,α为-1.627×109张 s·m g-1,E0为9.2张(P < 0.01);两药混合后的α分别为1.375×1010张 s·m g-1和-6.150×109张 s·m g-1,而E0为7.08张(P < 0.01);
    结论采用速效关系可线性化Hill量效方程,中药复方的有效性问题可采用体内外的速效关系模型进行研究。

     

    Abstract:
    ObjectiveTo explore the velocity-effect relationship in order to the establish linearization of effect on an equation with regard to the consistency of the Hill dose-effect expression with the metabolic kinetics of receptors.
    MethodsThe linear velocity-effect expression was obtained by solving multivariant differential equation groups, which were established to compare the coincidences and basic relations between the Hill dose-effect and metabolic kinetic Michaelis-Menten equation for receptors. The validation test was conducted with acetylcholine, adrenaline, and their mixture as model drugs.
    ResultsThe linear velocity-effect modelling was represented in vivo or in vitro, for single and multidrug systems. Pharmacodynamic parameters, especially suitable for multicomponent CMM formulas, could be determined and calculated for single or multicomponent formulas at high saturating or low linear concentration for receptors. The validation test showed that the pharmacodynamic parameters of acetylcholine were: k, 2.675×10-3 s-1; ka, 5.786×10-9 s-1; km, 2.500×10-7 s-1; α, 4.619×109张 s·m g-1; E0, 13张(P < 0.01) and those of adrenaline were: k, 1.415×10-3 s-1; ka, 5.846×10-9 s-1; km, 2.300×10-7 s-1; α, -1.627×109张 s·m g-1; E0, 9.2张(P < 0.01). For the mixture of the two components, the values were: α, 1.375×1010张 s·m g-1; -6.150×109张 s m g-1 for acetylcholine and adrenaline, respectively, and E0 was 7.08张in both, with the other parameters unchanged (P < 0.01).
    ConclusionThe velocity-effect equation can linearize the Hill dose-effect relationship, which can be applied to study the pharmacodynamics and availability of CMM formulations in vivo and in vitro.

     

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