In the well-stirred hepatic clearance equation, if fu × CLint is much greater than Q, ClH approximates to which?

• A. Q
• B. fu × CLint
• C. ClH
• D. 0

Answer: (A)

The main idea here is how hepatic clearance shifts with the relative size of intrinsic clearance times unbound drug compared to liver blood flow. In the well-stirred model, ClH = (Q × fu × CLint) / (Q + fu × CLint). If fu × CLint is much larger than Q, the denominator is dominated by fu × CLint, so ClH ≈ (Q × fu × CLint) / (fu × CLint) = Q. That means the liver can extract nearly all the drug as it passes through, and the clearance is limited by the blood flow to the liver rather than the enzyme capacity. In contrast, if fu × CLint were much smaller than Q, ClH would approximate fu × CLint. So the correct result in this scenario is that hepatic clearance approaches Q.