Example : A new antiarrhythmic drug which is completely metabolized by the liver has hepatic extraction ratio of 0.1 in a patient whose liver blood flow is 1.5 L/min. Discuss the effect of decreasing the liver blood flow 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 low extraction ratio drug

Intrinsic clearance :

The change in hepatic blood flow does not affect the liver capacity for drug metabolism, and does not affect the Intrinsic clearance.

Hepatic extraction ratio :

The decrease in liver blood flow increases the hepatic extraction ratio.

Total body clearance :

The increase in the extraction ratio due to the decrease in liver blood flow will not have a significant effect on the hepatic clearance which represents the total body clearance in this drug. This is because the product of the hepatic extraction ratio and the liver blood flow will not change significantly.

Oral bioavailability :

The increase in the extraction ratio will not have a significant effect on the bioavailability and the plasma conc-time profile.

Answer :

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