Pharmacy PEBC Practice Exam

The first-pass effect refers to the metabolic process that occurs when a drug is administered orally and passes through the gastrointestinal tract and liver before entering systemic circulation. During this process, a significant portion of the drug may be metabolized into inactive forms or significantly reduced in concentration due to enzymatic activity, primarily in the liver.

As a result, the amount of the active drug that reaches the systemic circulation can be much lower than the initial dose administered. This reduction in the amount of unchanged drug that ultimately circulates in the bloodstream is why the first-pass effect has a decreasing impact on a drug's bioavailability, which is defined as the proportion of the drug that enters the systemic circulation in a pharmacologically active form.

In essence, a drug that undergoes extensive first-pass metabolism may have a low bioavailability, meaning that less of the drug is available to exert its therapeutic effects. Therefore, the first-pass effect significantly reduces a drug’s bioavailability, confirming that the correct answer is that it decreases bioavailability.