First Pass Metabolism (Presystemic Hepatic Metabolism)
Definition
- First Pass Hepatic Metabolism refers to metabolism of a drug during its passage from the site of absorption into the systemic circulation.
- When a drug is absorbed from the GI tract, it enters the portal circulation before entering the systemic circulation. If the drug is rapidly metabolized in the liver or gut wall during this initial passage, the amount of unchanged drug entering the systemic circulation is decreased. This is referred to as first-pass metabolism.
- All orally administered drug are exposed to drug metabolizing enzymes in the intestinal wall and liver (where they first reach through the portal vein).
- Presystemic metabolism of limited magnitude can also occur in the skin (transdermally administered drug) and in lungs (for drug reaching venous blood through any route).
Extent of first pass metabolism
- The extent of first pass metabolism differs for different drugs and is an important determinant of oral bioavailability.
- For example, more than 90% of nitroglycerin is cleared during first-pass metabolism. Hence, it is primarily administered via the sublingual or transdermal route.
- Drugs with high first-pass metabolism should be given in doses sufficient to ensure that enough active drug reaches the desired site of
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Attributes of drugs with high first pass metabolism:
- Oral dose is considerably higher than sublingual or parenteral dose.
- There is marked individual variation in the oral dose due to differences in the extent of first pass metabolism.
- Oral bioavailability is apparently increased in patients with severe liver disease.
- Oral bioavailability of a drug is increased if another drug competing with it in first pass metabolism is given concurrently, e.g. chlorpromazine and propranolol.
