3.6:
Factors Influencing Bioavailability: First-Pass Elimination
An orally administered drug is absorbed across the GI tract, then flows through the portal vein into the liver before entering the systemic circulation.
The drug is primarily metabolized in the liver and sometimes in the gut wall.
So, the amount of drug reaching the systemic circulation, that is, the bioavailability of the drug, reduces substantially.
Bioavailability depends on several factors, of which metabolism by the liver or gut, or the first-pass metabolism is the most prominent.
Other factors include chemical stability, drug solubility and formulation.
Drugs that are chemically unstable in the stomach pH or are prone to enzymatic degradation break down in the GI tract.
Highly hydrophobic drugs cannot dissolve in aqueous body fluids, whereas highly hydrophilic drugs cannot cross the lipid bilayer of cells and are poorly absorbed.
Drug formulation influences bioavailability by affecting drug dissolution. Minimizing drug particle size, using a drug's salt, crystal, or hydrate form or adding enteric coatings can help drugs get easily dissolved and increase their bioavailability.
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.