In the well-stirred hepatic clearance model, CLint represents what?

• A. Hepatic blood flow.
• B. Fraction unbound in plasma.
• C. Intrinsic hepatic clearance; rate of metabolism independent of blood flow.
• D. Renal clearance.

Answer: (C)

Intrinsic clearance is the liver’s inherent ability to metabolize a drug by its enzymes, measured as the rate of metabolism when the drug has unimpeded access to the hepatic metabolic machinery and is not limited by blood flow or binding. In the well-stirred liver model, this intrinsic capacity (CLint) combines with hepatic blood flow and the fraction unbound in plasma to give the actual hepatic clearance: CLh = (Qh × fu × CLint) / (Qh + fu × CLint). Because CLint reflects the enzyme-driven metabolism, it is determined by enzyme kinetics and tissue metabolism, not by how quickly blood delivers drug to the liver. If the intrinsic clearance is very high relative to blood flow, clearance approaches the hepatic blood flow; if it is low, clearance is limited by the amount of drug delivered and available for metabolism. The other model factors—hepatic blood flow (Qh) and fraction unbound (fu)—influence the outcome but do not represent the liver’s metabolic capacity itself.