Nies A S, Shand D G, Wilkinson G R
Clin Pharmacokinet. 1976;1(2):135-55. doi: 10.2165/00003088-197601020-00005.
For some drugs, delivery to the liver by the hepatic circulation is an important determinant of removal by this organ. Classical pharmacokinetic analyses cannot predict the changes produced by altering any of the biological determinants of drug elimination by the liver; hepatic blood flow, metabolic enzyme activity, drug binding and route of administration. However, with the use of a physiological model of hepatic drug elimination, such predictions can be made. This model has been tested experimentally and appears to be valid. Hepatic blood flow can vary over about a 4-fold range from half normal flow to twice logical changes affecting the circulation. For drug clearance to be affected significantly by these changes in flow, the drug must be avidly removed by the liver as reflected in a high hepatic extraction ratio and intrinsic hepatic clearance. This latter term is a useful way to characterise the ability of the liver to irreversibly remove drug from the circulation in the absence of any flow limitation. The clearance of drugs with low intrinsic clearance will not be affected significantly by changes in liver blood flow.
对于某些药物，经肝循环输送至肝脏是该器官清除药物的一个重要决定因素。传统的药代动力学分析无法预测通过改变肝脏药物消除的任何生物学决定因素（肝血流量、代谢酶活性、药物结合及给药途径）所产生的变化。然而，使用肝脏药物消除的生理模型则可以进行此类预测。该模型已通过实验验证，似乎是有效的。肝血流量可在约4倍的范围内变化，从正常血流量的一半至两倍，这些逻辑变化会影响循环。要使药物清除率因这些血流变化而受到显著影响，该药物必须被肝脏大量清除，这反映在高肝提取率和肝固有清除率上。后一个术语是一种有用的方式，用于表征肝脏在不存在任何血流限制的情况下从循环中不可逆地清除药物的能力。肝固有清除率低的药物的清除率不会因肝血流量的变化而受到显著影响。
