Disposition of drugs, which are primarily metabolized by the liver, will be influenced in chronic liver disease by the following factors: intrinsic clearance, liver blood flow, and shunt volume. This group of drugs may be divided in two subgroups: (a) drugs with a high clearance, a high extraction rate and a short biological half-time, and (b) drug with a low clearance, a low extraction rate, and a long biological half-time. A high extraction rate means a low systemic bioavailability, since a rather big proportion of the drug will be eliminated after oral intake already during the first pass through the liver (= first past effect). In liver cirrhosis bioavailability may be increased manifold because of the portosystemic shunting. Thus there is the danger of overdosage in group (a) drugs because of two mechanisms: reduced elimination and increased bioavailability.