Macheras P
Department of Pharmacy, University of Athens, Panepistimiopolis, Greece.
Pharm Res. 1995 Apr;12(4):541-8. doi: 10.1023/a:1016201929304.
A model based on the fractal methodology is proposed for the kinetic study of carrier-mediated transport under heterogeneous conditions, i.e., when the drug-carrier interaction occurs at an interface with an effective dimensionality smaller than the embedding dimension of d = 2. A model equation is derived for the flux, based on a similar approach for an analogous equation for enzyme kinetics. It is shown that the total flux-solute concentration plots are curvilinear when the fractal dimension is smaller than unity while they become biexponential, with ascending and descending limbs, when the fractal dimension D is in the range 1 < D < 2. Nonlinear Lineweaver-Burk plots are obtained when this fractal kinetics approach is used. Good fittings are obtained when the fractal model is applied to literature data previously analysed with a combined transport mechanism, revealing experimental systems that display a D value in the range 1 < D < 2. It is suggested that transport studies should be carried out at a wider working solute concentration range and various agitation and incubation conditions in order to derive definite conclusions for the transport pathways.
提出了一种基于分形方法的模型,用于非均相条件下载体介导运输的动力学研究,即当药物-载体相互作用发生在有效维度小于嵌入维度d = 2的界面时。基于与酶动力学类似方程的相似方法,推导了通量的模型方程。结果表明,当分形维数小于1时,总通量-溶质浓度曲线是曲线形的,而当分形维数D在1 < D < 2范围内时,它们变为双指数曲线,有上升和下降分支。当使用这种分形动力学方法时,可得到非线性的Lineweaver-Burk图。将分形模型应用于先前用联合运输机制分析的文献数据时,得到了良好的拟合结果,揭示了显示D值在1 < D < 2范围内的实验系统。建议应在更宽的工作溶质浓度范围以及各种搅拌和孵育条件下进行运输研究,以便对运输途径得出明确结论。