If intrinsic clearance CLint is reduced due to hepatic impairment, what happens to the extraction ratio EH when fu and Qh stay the same?

• A. EH increases.
• B. EH decreases.
• C. EH remains the same.
• D. EH becomes undefined.

Answer: (B)

Extraction ratio tells us what fraction of drug is removed by the liver in a single pass. In the well-stirred model, EH equals (fu × CLint) divided by (Qh + fu × CLint). If fu and hepatic blood flow Qh stay the same and intrinsic clearance CLint is reduced, the product fu × CLint becomes smaller. That lowers the numerator and also reduces the denominator, but the overall effect is a smaller ratio, so EH decreases. Intuitively, when the liver’s metabolic capacity drops, it clears less drug per pass, lowering the extraction ratio. As CLint becomes very low, EH approaches zero; as CLint is very high, EH approaches one.