Summary of the effect of changing the hepatic
intrinsic clearance on drug disposition

a- Low extraction ratio drugs :

The increase in intrinsic clearance results in a significant increase in E, hepatic clearance and the drug elimination rate for low extraction ratio drugs.

After oral administration of low extraction ratio drugs, the increase in intrinsic clearance results in a significant increase in E which will increase the hepatic clearance and the rate of drug elimination. However this increase in E will have a minor effect on the bioavailability of the drug because the bioavailability of these drugs is usually high.

b- High extraction ratio drugs:

The increase in intrinsic clearance does not significantly affect E, hepatic clearance and the elimination rate of high extraction ratio drugs after iv administration.

After oral administration of high extraction ratio drugs, the elimination rate does not change as a result of the increase in intrinsic clearance. However, the increase in intrinsic clearance results in slight increase in E which decreases the drug bioavailability. Because the bioavailability of high extraction ratio drugs is low any small change in bioavailability will result in significant change in the drug conc-time profile.