First pass effect

First pass effect or first pass metabolism refers to the phenomenon whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is a significant factor in the pharmacokinetics and pharmacodynamics of medications. This process occurs mainly in the liver, but also in the lungs, gastrointestinal tract, and blood vessels. Understanding the first pass effect is crucial for determining the appropriate route of administration for a drug, as it can significantly impact the drug's bioavailability.

Mechanism

The first pass effect involves the initial metabolism of a drug during its first journey from the site of administration into the systemic circulation. Oral medications, for example, are absorbed from the gastrointestinal tract and transported directly to the liver via the portal vein. In the liver, enzymes metabolize a significant portion of the drug into metabolites, which may be less active, inactive, or even toxic. The extent of this metabolism can vary greatly depending on the drug's chemical properties and the individual's genetic makeup.

Factors Influencing the First Pass Effect

Several factors can influence the extent of the first pass effect, including:

• The drug's chemical structure
• The individual's genetic makeup, which can affect enzyme levels and activity
• The presence of other drugs that may induce or inhibit the metabolizing enzymes
• The health of the liver and gastrointestinal tract

Clinical Implications

The first pass effect has several important clinical implications:

• It necessitates higher oral doses of some drugs compared to other routes of administration to achieve the desired therapeutic effect.
• It can lead to significant variability in drug response among individuals.
• It can influence the choice of drug formulation and route of administration.

Managing the First Pass Effect

To manage the first pass effect, pharmaceutical companies may:

• Develop drugs that are less susceptible to hepatic metabolism.
• Use alternative routes of administration (e.g., sublingual, intravenous) that bypass the liver.
• Modify drug formulations to protect the drug from metabolism during its first pass through the liver.

See Also

• Bioavailability
• Drug metabolism
• Pharmacokinetics
• Route of administration