16th May 2025

Impairment of drug metabolism

The liver is the main site of drug metabolism in the body. Many drugs that are taken orally undergo a first pass metabolism, which reduces the concentration of the active drug reaching its site of action. In liver disease first pass metabolism is diminished which can result in increased circulating levels of active drugs in the body.

Other drugs are administered as a prodrug (e.g. clopidogrel, enalapril, and oxcarbazepine) which are inactive until they undergo metabolism in the liver. If the liver isn’t functioning correctly there may be decreased activity of these medications as less of the prodrug will be converted to its pharmacologically active form.

It is worth noting that routine liver function tests are not a reliable marker of the ability of the liver to metabolise drugs, it can be difficult to predict the extent that a drug’s metabolism may be impaired in an individual patient.