AEMCA Practice Exam

What causes a dramatic decrease in systemic availability of a drug following oral administration?

1. The drug's high water solubility

2. The passive absorption process

3. The first-pass effect by the liver

4. The chemical stability of the drug in the gastrointestinal tract

The correct answer is: The first-pass effect by the liver

The dramatic decrease in systemic availability of a drug following oral administration is primarily attributed to the first-pass effect by the liver. When a drug is ingested orally, it is absorbed through the gastrointestinal tract and then enters the portal circulation, which leads to the liver. The liver metabolizes a significant portion of the drug before it enters the systemic circulation; this process can significantly reduce the effective concentration of the drug that reaches the bloodstream. As a result, the bioavailability of the drug—the proportion of the administered dose that reaches systemic circulation—is reduced. In contrast, factors such as the drug's solubility, absorption processes, and chemical stability can influence absorption but may not primarily account for the substantial decrease in drug availability seen after liver metabolism. For example, while high water solubility can enhance a drug's absorption, it does not counteract the metabolic processes occurring in the liver. Therefore, understanding the first-pass effect is crucial for recognizing how oral medications can require higher doses to achieve therapeutic effects compared to other routes of administration, like intravenous delivery.