It is the volume of the plasma or the blood completely cleared from the drug/unit time by the liver. It has units of volume/time.

The hepatic clearance cannot exceed the total body clearance. However it can be equal to the total body clearance when the drug is excreted completely by the liver.

The hepatic clearance can be determined from the liver blood flow and the hepatic extraction ratio ( CL_H= Q-_hepatic• B).

It is the maximum ability of the liver to eliminate the drug in absence of any flow limitation. It has units of volume/time. Based on this definition the hepatic clearance can be as high as the intrinsic clearance but it cannot be higher than it.

The hepatic intrinsic clearance is a measure of the amount of the enzymes available for drug metabolism. Enzyme induction increases the total amount of enzymes available for drug metabolism leading to higher hepatic intrinsic clearance. On the other hand liver diseases that will alter the ability of the liver to eliminate the drug decrease the hepatic intrinsic clearance.

For low extraction ratio drugs, the hepatic intrinsic clearance is close to the hepatic clearance, and for high extraction ratio drugs the intrinsic clearance is much higher than the hepatic clearance.

Enzyme induction means increasing the metabolic activity of the enzyme system. This can happen by a wide variety of agents known as enzyme inducers. Enzyme inducers usually increase enzyme synthesis leading to higher amount of the enzyme and increase in the capacity of one or more metabolic pathway.

The consequence of enzyme induction on drug metabolism depend on the drug. Some inducers are specific inducers of certain specific sub-family of CYP-450 which can affect the drugs metabolized by that particular CYP-450 sub-family.

Also drugs that are metabolized by high capacity metabolic pathways (high extraction ratio drugs, or drugs that have high intrinsic metabolic clearance) will not be affected significantly by enzyme inducers. On the other hand, enzyme induction significantly affect the rate of metabolism of drugs that have low intrinsic metabolic clearance (low extraction ratio drugs).