RLO: Introduction to drug clearance

Total drug clearance

Drug clearance involves both the processes of metabolism and excretion.

Metabolic - or hepatic - clearance is the conversion of the parent drug into a different chemical entity by liver enzymes, particularly the cytochrome P450 family of enzymes. It is dependent on a number of factors, including: hepatic blood flow, the rate of liver enzyme activity and the rate of secretion into the bile. Anything which impacts on these factors (eg. competition between drugs for the metabolising enzymes in the liver, or genetic polymorphisms which alter the activity of these enzymes) may, in turn, impact on drug clearance, either speeding it up or slowing it down.

The key point to remember about metabolism is that it makes drugs less lipid soluble, more water soluble, and therefore easier to excrete from the body.

Renal clearance, on the other hand, is the removal of the drug from the body by the kidneys. It is dependent on a number of factors, including: renal blood flow, and the rates of glomerular filtration and tubular secretion compared to the rate of passive diffusion. (Lipid soluble, or un-ionised drugs will undergo passive diffusion, being reabsorbed into the blood stream; ionised drugs will be retained within the tubule.) Anything which impacts on these factors may impact on drug clearance, either speeding it up or slowing it down.

 

When you've completed this section, click the next button button on the media player, or click the 'Hepatic clearance: Activity' tab above to continue.