Question: The hepatic clearance of a drug, mainly eliminated by metabolism, which has a high degree of hepatic extraction and a high binding to plasma proteins: 
 Options:  <1> It is significantly influenced by the hepatic blood flow. <2> It is significantly influenced by changes in the degree of plasma protein binding. <3> It is significantly influenced both by hepatic blood flow and by changes in the degree of plasma protein binding. <4> It will not be influenced by the hepatic blood flow or by changes in the degree of binding to plasma proteins. <5> It will depend on the absolute bioavailability of the drug.
1