Example : A new anticonvulsant drug which is completely metabolized by the liver has hepatic extraction ratio of 0.92 in a patient whose liver blood flow of 1.6 L/min. Discuss the effect of enzyme induction on hepatic intrinsic clearance, hepatic extraction ratio, total body clearance, and oral bioavailability. For each parameter determine if it significantly increases, significantly decreases, or does not change.

This is a high extraction ratio drug

Intrinsic clearance :

Enzyme induction increases the liver metabolic capacity which significantly increases the Intrinsic clearance of the drug.

Hepatic extraction ratio :

The increase in Intrinsic clearance due to enzyme induction does not lead to significant increase in the extraction ratio of high extraction ratio drugs.

Total body clearance :

The total body clearance of high extraction ratio drugs does not change significantly as a result of enzyme induction.

Oral bioavailability :

Enzyme induction causes slight increase in the extraction ratio. For high extraction ratio drugs, even slight increase in the extraction ratio will result in a significant relative decrease in the drug bioavailability.

Answer :

Intrinsic clearance : Increases significantly
Extraction ratio : Does not change significantly
Total body clearance : Does not change significantly
Oral bioavailability : Decreases significantly