Marsh Rebeccah E, Tuszyński Jack A
P-412, Avadh Bhatia Physics Laboratory, Department of Physics, Faculty of Science, University of Alberta, Edmonton, AB, T6G 2J1, Canada.
Pharm Res. 2006 Dec;23(12):2760-7. doi: 10.1007/s11095-006-9090-6. Epub 2006 Oct 25.
To provide the first application of fractal kinetics under steady state conditions to pharmacokinetics as a model for the enzymatic elimination of a drug from the body.
A one-compartment model following fractal Michaelis-Menten kinetics under a steady state is developed and applied to concentration-time data for the cardiac drug mibefradil in dogs. The model predicts a fractal reaction order and a power law asymptotic time-dependence of the drug concentration, therefore a mathematical relationship between the fractal reaction order and the power law exponent is derived. The goodness-of-fit of the model is assessed and compared to that of four other models suggested in the literature.
The proposed model provided the best fit to the data. In addition, it correctly predicted the power law shape of the tail of the concentration-time curve.
A simple one-compartment model with steady state fractal Michaelis-Menten kinetics describing drug elimination from the body most accurately describes the pharmacokinetics of mibefradil in dogs. The new fractal reaction order can be explained in terms of the complex geometry of the liver, the organ responsible for eliminating the drug.
首次将稳态条件下的分形动力学应用于药代动力学，作为药物从体内酶促消除的模型。
建立了一个遵循稳态下分形米氏动力学的单室模型，并将其应用于犬类心脏药物米贝拉地尔的浓度 - 时间数据。该模型预测了分形反应级数以及药物浓度的幂律渐近时间依赖性，因此推导了分形反应级数与幂律指数之间的数学关系。评估了该模型的拟合优度，并与文献中提出的其他四个模型进行了比较。
所提出的模型对数据拟合最佳。此外，它正确预测了浓度 - 时间曲线尾部的幂律形状。
一个具有稳态分形米氏动力学的简单单室模型，最准确地描述了米贝拉地尔在犬体内的药代动力学，该模型描述了药物从体内的消除过程。新的分形反应级数可以根据负责消除药物的肝脏的复杂几何结构来解释。
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