Which term in the well-stirred model represents the liver's capacity to clear drug in the unbound state?

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

Answer: (A)

In the well-stirred liver model, the liver’s capacity to clear drug when it is unbound is captured by the product of the unbound fraction and intrinsic clearance, fu × CLint. CLint is the liver’s enzymatic clearance capability when the drug is free of protein binding, and fu is the fraction of drug that remains unbound in plasma. Only the unbound drug is available for metabolism, so multiplying these two factors gives the intrinsic clearance available to the liver for the unbound drug. This term combines with hepatic blood flow to determine the actual hepatic clearance via the equation CLh = (Q × fu × CLint) / (Q + fu × CLint). The other terms describe different aspects: Q is blood flow delivering drug to the liver, Cin is not the standard model term, and ClH is the resulting hepatic clearance, not the liver’s unbound-capacity itself.