If a drug has a high hepatic extraction ratio, what is the likely effect on its oral bioavailability?

If a drug has a high hepatic extraction ratio, what is the likely effect on its oral bioavailability?

• A. Strongly limited by first-pass metabolism, leading to large loss
• B. Not affected by first-pass hepatic metabolism
• C. Increased by active transport into portal blood
• D. Decreased clearance in liver

Answer: (A)

The main idea is how first-pass liver metabolism affects oral exposure. A drug with a high hepatic extraction ratio is heavily removed by the liver as it travels from the gut to the systemic circulation. Because oral dosing delivers the drug to the portal vein first, extensive hepatic metabolism means only a small fraction escapes to the bloodstream. So oral bioavailability is greatly reduced, with large loss during the first pass. In other words, strong first-pass metabolism limits how much drug can reach systemic circulation after an oral dose.

The main idea is how first-pass liver metabolism affects oral exposure. A drug with a high hepatic extraction ratio is heavily removed by the liver as it travels from the gut to the systemic circulation. Because oral dosing delivers the drug to the portal vein first, extensive hepatic metabolism means only a small fraction escapes to the bloodstream. So oral bioavailability is greatly reduced, with large loss during the first pass. In other words, strong first-pass metabolism limits how much drug can reach systemic circulation after an oral dose.