Pharmacokinetics in liver disease.

Some general pharmacokinetic principles, relevant to understand and predict altered disposition of drugs in liver disease, are reviewed. It is appropriate to differentiate between high- and low-clearance drugs as to the influence of hepatic dysfunction. On intravenous administration high-clearance drugs generally show reduced systemic clearance predominantly caused by decreased liver blood flow, whereas on oral administration a considerable increase in systemic availability may occur caused by reduced enzyme activity and (in cirrhosis) bij portacaval shunting. Low-clearance drugs are sensitive to reduced enzyme activity and reduced protein binding. It seems that oxidative reactions are far more affected than conjugation reactions in liver disease. Large inter-patient variability exists in the kinetics of a drug in any type of hepatic disease. The conventional liver-function tests are of no value in predicting altered drug disposition.