Effect of hepatic insufficiency on pharmacokinetics and drug dosing

The liver plays a central role in the pharmacokinetics of many drugs. Liver dysfunction may not only reduce the plasma clearance of a number of drugs eliminated by biotransformation and/or biliary excretion, but it can also affect plasma protein binding which in turn could influence the processes of distribution and elimination. In addition, reduced liver blood flow in patients with chronic liver disease will decrease the systemic clearance of flow limited (high extraction) drugs and portal-systemic shunting may substantially reduce their presystemic elimination (first-pass effect) following oral administration. When selecting a drug and its dosage regimen for a patient with liver disease additional considerations such as altered pharmacodynamics and impaired renal excretion (hepatorenal syndrome) of drugs and metabolites should also be taken into account. Consequently, dosage reduction is necessary for many drugs administered to patients with chronic liver disease such as liver cirrhosis.