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.

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.

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).

The extraction ratio is the fraction of the drug presented to the organ which is eliminated during a single pass through the organ.

The extraction ratio can have values between 0 and 1 (or 0% - 100%). It is zero when the drug is not eliminated by the organ, and it is 1 when all the drug presented to the organ is eliminated during a single pass.

The extraction ratio does not have units.

Bioavailability is a measure of the fraction of the administered dose that reaches the systemic circulation.

Absolute bioavailability is the fraction of the total dose that reaches the systemic circulation. It can have values between zero when the drug is not absorbed at all to 1 when all the administered dose reaches the systemic circulation. The absolute bioavailability can be expressed in terms of percentage (0% - 100%).

The relative bioavailability is the bioavailability of a drug product relative to the bioavailability of another drug product (reference standard preparation). The relative bioavailability can take any value above zero. It can be more than one when the product under investigation has bioavailability higher than that of the reference standard.

The fraction of the dose that reaches the systemic circulation (bioavailable drug) is the fraction of the dose that escapes hydrolysis and metabolism in the gut lumen, metabolism in the gut wall, and metabolism during the first pass through the liver. Elimination of the drug before it reaches the systemic circulation is called presystemic elimination or first-pass effect.

This relationship is true only if the drug is completely (100%) absorbed into the portal circulation and the only cause for incomplete bioavailability is the hepatic metabolism during the first-pass through the liver.