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A decrease in hepatocellular function decreases the capacity of the liver to perform metabolic processes, while portosystemic shunting directs drugs away from sites of metabolism. Both factors are usually present in patients with severe cirrhosis.

Knowledge of the drugs that undergo first‐pass metabolism is important in situations where it is decreased as a result of disease. Considerably greater quantities of active drug then reach the site of action and any given dose of drug has unexpectedly intense effects.

Examples of changes in bioavailability found in some patients with severe cirrhosis are:

 Clomethiazole (chlormethiazole) (100% increase)

 Labetalol (91% increase)

 Metoprolol (65% increase)

 Nicardipine (500% increase)

 Paracetamol (50% increase)

 Propranolol (42% increase)

 Verapamil (140% increase)

Conversely, first‐pass activation of pro‐drugs such as many ACE inhibitors (e.g. enalapril, perindopril, quinapril) may potentially be slowed or reduced.