Intrinsic clearance

Intrinsic clearance (Cl_int) is a theoretical clearance value that gives an indication of how efficiently a drug is metabolised by liver enzymes. The units of Cl_int are litres/hour. It is the volume of blood (containing a saturating concentration of drug) that you could theoretically flow through the liver every hour such that the liver is still capable of removing essentially all of the drug.

Click here to view a short animation that provides an explanation of the meaning of Cl_int.

For example, glyceryl trinitrate is removed very rapidly by liver enzymes. At a regular liver blood flow rate of 90 litres/hour, the liver has no problem removing virtually all of the glyceryl trinitrate. Imagine it was possible to increase the blood flow through the liver (and therefore increase the supply of glyceryl trinitrate to the liver) to a rate of 10,000 litres/hour before E_H starts to fall below 1 (i.e. before the liver enzymes reach the point when they are no longer able to metabolise all of the glyceryl trinitrate being delivered to the hepatocytes in the blood stream), and unmetabolised drug starts to escape the liver. This 10,000 litres/hour value would then be (approximately) equal to the intrinsic clearance for glyceryl trinitrate. In this example, Cl_int is clearly very much larger than the hepatic blood flow of 90 litres/hour – it is a theoretical value. So if we then calculate the value for the hepatic extraction ratio, and we assume that f_u is 100%, we can see that this results in a value for E_H of close to 1.

Thereafter, we calculate the hepatic clearance for glyceryl trinitrate, from Cl_H = Q_H x E_H, as 90 l/h x 0.991 = 89 litres/hour. From this example you can see how it is necessary for the intrinsic clearance of a drug, Cl_int, to be very high in order for the hepatic clearance of that drug to be high (close to 90 l/h), and why the hepatic clearance can’t exceed 90 litres/hour, even when intrinsic clearance is very much higher than that.