Wach P, Trajanoski Z, Kotanko P, Skrabal F
Institute of Biomedical Engineering, Graz University of Technology, Austria.
Med Biol Eng Comput. 1995 Jan;33(1):18-23. doi: 10.1007/BF02522939.
A pharmacokinetic model is modified to enable quantitation of subcutaneous insulin absorption following insulin injections of soluble insulin and monomeric insulin analogues. The model for soluble insulin includes diffusion, equilibration between hexameric and dimeric insulin and absorption of dimeric insulin molecules. Numerical approximation is carried out by modelling the whole system as a capacitor-resistor network with lumped elements and discrete sources and sinks. By means of the analytical solution for monomeric-insulin absorption, it can be shown that the approximation scheme yields sufficiently accurate results. The modified model for soluble insulin demonstrates dose- and concentration-dependent insulin absorption within the range of therapeutic concentrations and volumes. Additionally, parameters are estimated from published glucose-clamp data. The results of the data fitting indicate that the model presented is adequate for pharmacological studies. The model is suitable for individual parameter estimation from the time course of plasma insulin or from the disappearance curves of radiolabelled injected insulin.
对药代动力学模型进行了修改，以实现对可溶性胰岛素和单体胰岛素类似物注射后皮下胰岛素吸收的定量分析。可溶性胰岛素模型包括扩散、六聚体胰岛素与二聚体胰岛素之间的平衡以及二聚体胰岛素分子的吸收。通过将整个系统建模为具有集总元件以及离散源和汇的电容 - 电阻网络来进行数值近似。借助单体胰岛素吸收的解析解，可以证明该近似方案能产生足够准确的结果。修改后的可溶性胰岛素模型在治疗浓度和体积范围内显示出剂量和浓度依赖性胰岛素吸收。此外，根据已发表的葡萄糖钳夹数据估计参数。数据拟合结果表明所提出的模型适用于药理学研究。该模型适用于根据血浆胰岛素的时间进程或放射性标记注射胰岛素的消失曲线进行个体参数估计。
