3.6 : Factors Influencing Bioavailability: First-Pass Elimination

When a drug is taken orally, it undergoes a journey starting from the gastrointestinal (GI) tract, passing through the portal vein, reaching the liver, and finally entering the systemic circulation. This process involves the absorption of the drug across the GI tract. The liver is the primary site for metabolizing the drug, with some metabolism also occurring in the gut wall. This journey significantly reduces the quantity of the drug that reaches the systemic circulation, a phenomenon known as the drug's bioavailability.

Bioavailability is influenced by multiple factors, including the drug's first-pass metabolism in the liver or gut. Other factors shaping bioavailability include the chemical stability of the drug, its solubility, and its specific formulation. For instance, drugs that are chemically unstable in the stomach pH or susceptible to enzymatic degradation tend to disintegrate within the GI tract. Highly hydrophobic drugs struggle to dissolve in the body's water-based fluids, while highly hydrophilic drugs find it difficult to pass through cell lipid bilayers, resulting in poor absorption. Additionally, the drug's formulation can also impact bioavailability. Strategies like reducing drug particle size, using the drug in its salt, crystal, or hydrate form, or adding enteric coatings can enhance dissolution, thereby increasing bioavailability.