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).

The increase in intrinsic clearance results in small increase in the extraction ratio. This will not affect the hepatic clearance, total body clearance, half life, and AUC significantly.

Although the increase in extraction ratio is small, the change in bioavailability will have a significant effect on the plasma conc-time profile. The increase in extraction ratio from 0.9 to 0.95 will result in a decrease in bioavallability from 0.1 to 0.05. This will decrease the drug AUC by 50%.