Low hepatic extraction ratio drug

A drug which is a poor substrate for liver enzymes and therefore which has a low intrinsic clearance. The hepatic clearance of these drugs is usually low (less than 10 litres/hour) and oral bioavailability is high (greater than 90%). Changing Cl_int (by inhibiting or inducing hepatic enzymes) has a small relative effect on the oral bioavailability of these drugs but has a large relative effect on their hepatic clearance (see discussion of this point under the entry for high hepatic extraction ratio drugs). Note that while hepatic clearance may be low, total body clearance could still be high if the drug is removed efficiently and extensively by the kidneys. As a result, a large change in Cl_int may have very little effect on total body clearance, Cl_T, even if the relative effect on hepatic clearance is quite large, because hepatic clearance may make such a small contribution to total clearance.