High hepatic extraction ratio drug
A drug which is a very good substrate for liver enzymes and therefore which has a high intrinsic clearance. The hepatic clearance of these drugs is usually high (close to the maximum possible hepatic clearance of 90 litres/hour) and oral bioavailability is usually low.
Changing Clint (by inhibiting or inducing hepatic enzymes) has a small relative effect on the hepatic clearance of these drugs. For example, doubling Clint may increase hepatic clearance from 81 l/h (where 90 mg of a 100 mg dose is removed) to 86 l/h (where 95mg of a 100 mg dose is removed). This is a small relative change in hepatic clearance. But the relative effect on bioavailability of that 5mg that does NOT now escape from the liver is substantial (10 mg did reach the systemic circulation before, but when Clint is doubled, only 5 mg are now able to do so). So the relative effect on the oral bioavailability of a high extraction ratio drug of changing Clint is large.
For a high hepatic extraction ratio drug in an individual patient, the effect of a change in Clint would be seen as a change in the AUC of a plasma concentration versus time graph for the same dose of the same drug administered orally, with little change in the elimination half life apparent on the latter portions of the curve. This would reflect an altered oral bioavailability but with little change in clearance.
