How does first-pass hepatic metabolism affect oral bioavailability, and which drugs show the greatest loss?

How does first-pass hepatic metabolism affect oral bioavailability, and which drugs show the greatest loss?

• A. It increases the fraction reaching systemic circulation; low extraction ratio drugs show minimal loss.
• B. It only affects IV dosing, not oral dosing.
• C. It has no effect on bioavailability.
• D. It reduces the fraction of drug reaching systemic circulation; drugs with high hepatic extraction ratios show substantial first-pass loss.

Answer: (D)

First-pass hepatic metabolism reduces the amount of drug that reaches systemic circulation after oral administration. As an orally absorbed drug travels through the portal vein to the liver, liver enzymes metabolize a portion of it before it enters the bloodstream, lowering oral bioavailability. The extent depends on the hepatic extraction ratio: drugs with a high extraction ratio are extensively cleared on this first pass, leading to substantial loss of bioavailability. In contrast, drugs with a low extraction ratio are less affected and retain more of their dose as they reach systemic circulation. That’s why the statement describing a reduction in the fraction reaching systemic circulation and noting substantial first-pass loss for high extraction ratio drugs is the best answer.

First-pass hepatic metabolism reduces the amount of drug that reaches systemic circulation after oral administration. As an orally absorbed drug travels through the portal vein to the liver, liver enzymes metabolize a portion of it before it enters the bloodstream, lowering oral bioavailability. The extent depends on the hepatic extraction ratio: drugs with a high extraction ratio are extensively cleared on this first pass, leading to substantial loss of bioavailability. In contrast, drugs with a low extraction ratio are less affected and retain more of their dose as they reach systemic circulation. That’s why the statement describing a reduction in the fraction reaching systemic circulation and noting substantial first-pass loss for high extraction ratio drugs is the best answer.