Presystemic metabolism

Presystemic metabolism, also known as first-pass metabolism, refers to the process where a drug is metabolized at a specific location in the body before it reaches systemic circulation. This process mainly occurs in the liver and, to some extent, in the gastrointestinal tract after oral administration of a drug.

1. Absorption: When a drug is ingested orally, it is absorbed through the walls of the stomach and small intestine.
2. Transport to the liver: The absorbed drug is transported via the portal vein to the liver before entering the general bloodstream.
3. Metabolism in the liver: In the liver, enzymes break down the drug, and depending on how much of the drug is metabolized, only a portion may become bioavailable (available to produce its therapeutic effects).
4. Reduced drug concentration: As a result, the drug’s concentration in the bloodstream is often lower than the original dose due to this metabolism before it enters systemic circulation.

Consequences of presystemic metabolism:

• It can reduce the bioavailability of certain drugs, requiring higher doses or alternative administration routes (like intravenous injection).
• The drug may become inactive or less effective before it even has a chance to reach its target.

Some common examples include medications like morphine or nitroglycerin, which undergo significant first-pass metabolism, necessitating alternative routes like injections or sublingual (under the tongue) administration for better effectiveness.