Roberts M S, Rowland M
J Pharmacokinet Biopharm. 1986 Jun;14(3):227-60. doi: 10.1007/BF01106706.
A dispersion model of hepatic elimination, based on the residence time distribution of blood elements within the liver, is presented. The general rate equations appropriate for describing the hepatic output concentration of a tracer solute are derived. Particular consideration is given to events following a bolus input dose of a tracer. The model is shown to be compatible with the known hepatic architecture and hepatic physiology. The model has been fitted to hepatic outflow data for red blood cells, albumin, and other noneliminated solutes. The experimental data suggest a high degree of dispersion of blood elements within the liver. The model has also been used to evaluate the effects of changes in enzyme activity, hepatic cell permeability, blood flow, and protein binding on the outflow concentration vs. time profiles of solutes.
本文提出了一种基于肝脏内血液成分停留时间分布的肝脏消除弥散模型。推导了适用于描述示踪溶质肝脏输出浓度的一般速率方程。特别考虑了示踪剂单次静脉注射剂量后的情况。该模型与已知的肝脏结构和肝脏生理学相符。该模型已被拟合到红细胞、白蛋白和其他非消除性溶质的肝脏流出数据。实验数据表明肝脏内血液成分存在高度弥散。该模型还被用于评估酶活性、肝细胞通透性、血流量和蛋白质结合的变化对溶质流出浓度与时间曲线的影响。
