Meier P J
Schweiz Med Wochenschr. 1982 Feb 20;112(8):258-63.
Patients with liver disease often show unusual responses to "standard" doses of drugs. Increased variability of response to drugs which are predominantly eliminated by the liver is mainly due to altered pharmacokinetics in the presence of hepatic dysfunction. The possible prediction of abnormal pharmacokinetics in hepatic disease requires a knowledge of the pharmacokinetic characteristics of a particular drug in healthy subjects and of the major pathophysiologic alterations which occur in a given form of liver disease. In all cases with significant impairment of the metabolic capacity of the liver (e.g. acute viral hepatitis), dosage adjustments should be based on decreased (hepatic) clearance rather than on prolongation of halflife of the respective drug. In addition, oral doses of those drugs which under normal conditions are efficiently extracted from sinusoidal blood by hepatocytes should be further reduced in chronic liver disease (e.g. cirrhosis) as marked increases in their systemic bioavailability occur in the presence of altered hepatic blood flow.
肝病患者对“标准”剂量的药物常常表现出异常反应。主要经肝脏消除的药物，其反应变异性增加主要是由于肝功能不全时药代动力学改变所致。预测肝病时异常药代动力学需要了解特定药物在健康受试者中的药代动力学特征以及特定形式肝病中发生的主要病理生理改变。在所有肝脏代谢能力显著受损的情况下（如急性病毒性肝炎），剂量调整应基于（肝脏）清除率降低，而非基于相应药物半衰期的延长。此外，在慢性肝病（如肝硬化）中，那些在正常情况下能被肝细胞从肝血窦血液中有效摄取的药物，口服剂量应进一步降低，因为在肝血流改变时其全身生物利用度会显著增加。
