In the well-stirred hepatic model, if fu*CLint >> Qh, CLh is approximately equal to which?

• A. fu*CLint
• B. Qh
• C. fu*CLint + Qh
• D. 0

Answer: (B)

In the well-stirred hepatic model, hepatic clearance depends on both hepatic blood flow and the intrinsic ability of the liver to clear drug, described by CL_h = (Q_h × fu × CL_int) / (Q_h + fu × CL_int). If fu × CL_int is much larger than Q_h, the term fu × CL_int dominates the denominator, so CL_h ≈ (Q_h × fu × CL_int) / (fu × CL_int) = Q_h. This means the liver clears drug at the rate determined by how fast blood can flow through it, i.e., flow-limited clearance. The extraction ratio in this case approaches 1. In other scenarios, if fu × CL_int is much smaller than Q_h, CL_h ≈ fu × CL_int (low extraction).