Which variables determine hepatic clearance in the well-stirred model?

• A. Q, fu, and CLint
• B. Q and fu only
• C. fu and CLint only
• D. Q, fu, CLint, and patient weight

Answer: (A)

In the well-stirred liver model, hepatic clearance is determined by three factors: liver blood flow (Q), the fraction of drug unbound in plasma (fu), and the intrinsic clearance capacity of the liver (CLint). The relationship is captured by the equation CLh = (Q × fu × CLint) / (Q + fu × CLint). This shows how delivery to the liver (Q), how much drug is actually available for metabolism (fu), and how efficiently the liver can metabolize the drug (CLint) all shape the final clearance.

If intrinsic clearance is very high relative to Q and fu, clearance approaches the liver’s blood flow (high extraction). If intrinsic clearance is low, clearance is limited by enzymatic capacity (low extraction). The fraction unbound is crucial because only unbound drug can be cleared. Patient weight doesn’t appear as a direct variable in this model; it would influence clearance only indirectly through effects on Q, fu, or CLint, not as a fundamental term in the well-stirred equation.

So, the variables that determine hepatic clearance in this model are Q, fu, and CLint.