Summary of the effect of changing the hepatic
blood flow on drug disposition

a- Low extraction ratio drugs :

The elimination rate of low extraction ratio drugs is affected by changes in the intrinsic clearance and it is not affected by changes in the hepatic blood flow. So, the change in hepatic blood flow has very minor effect on the total body clearance and the systemic bioavailability of these drugs and will not affect their plasma conc-time profile significantly.

b- High extraction ratio drugs:

The hepatic elimination rate of high extraction ratio drugs is dependent on the amount of the drug delivered to the liver which is dependent on the liver blood flow. The increase in liver blood flow will result in significant increase in the drug elimination rate and total body clearance after iv administration.

After oral administration of high extraction ratio drugs, the elimination rate increases due to the increase in hepatic blood flow. However, the increase in blood flow decreases E which leads to an increase the bioavailability. Because the bioavailability of high extraction ratio drugs is very low any small change in bioavailability will result in significant change in the drug conc-time profile.

So, the decrease in AUC due to the increase in drug clearance will be compensated by the increase in AUC due to the increased bioavailability.