In the well-stirred hepatic clearance model, if fu*CLint is much smaller than Qh, the hepatic clearance CLh is approximately equal to which quantity?

• A. fu*CLint
• B. Qh
• C. fu*CLint + Qh
• D. Qh - fu*CLint

Answer: (A)

In the well-stirred hepatic clearance model, the clearance is determined by both liver blood flow and intrinsic clearance, with only the unbound drug being available for metabolism. The relationship is CLh = (Qh × fu × CLint) / (Qh + fu × CLint). If fu × CLint is much smaller than Qh, the denominator is effectively Qh, so CLh ≈ (Qh × fu × CLint) / Qh = fu × CLint. This means the liver’s capacity to metabolize (intrinsic clearance) is the limiting factor, not the blood flow. Therefore, hepatic clearance is approximately fu × CLint.