RLO: Introduction to drug clearance

Relative importance of metabolism and excretion in drug clearance

The relative importance of metabolic and renal clearance differs, depending on the drug. Some drugs undergo mainly metabolic clearance, and others undergo mainly renal clearance.

One of the key factors which determine the importance of hepatic vs renal clearance is a particular drug's lipid solubility, or degree of ionisation..

As cell membranes are lipid in nature, lipid soluble (or un-ionised) drugs can readily cross them. These drugs will enter hepatocytes (or liver cells), and are likely to undergo extensive hepatic clearance.

However, if a drug is ionised, it will not be able to cross the membranes of liver cells easily. Therefore, this drug will be less likely to undergo hepatic metabolism, and more likely to undergo extensive renal clearance. Examples of drugs cleared almost entirely by the kidneys are furosemide and atenolol.

 

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