Write the hepatic clearance equation from the well-stirred model.

• A. ClH = (Q × fu × CLint) / (Q + fu × CLint)
• B. ClH = Q × fu × CLint
• C. ClH = Q / (fu × CLint)
• D. ClH = (Q + fu × CLint) / (Q × fu × CLint)

Answer: (A)

Hepatic clearance in the well-stirred model depends on the liver’s blood supply, the amount of drug that can actually be metabolized (unbound), and the liver’s intrinsic capacity to metabolize that drug. The equation is ClH = (Q × fu × CLint) / (Q + fu × CLint). Here Q is hepatic blood flow, fu is the fraction unbound in blood, and CLint is the intrinsic clearance by hepatic enzymes (the liver’s metabolic capacity for the unbound drug). The product fu × CLint represents the unbound intrinsic clearance.

The denominator combines both delivery and capacity; when fu × CLint is much larger than Q, the clearance approaches Q, meaning the liver is flow-limited. When fu × CLint is much smaller than Q, the clearance approaches fu × CLint, meaning the liver is capacity-limited. This form accurately describes how clearance depends on both how much drug reaches the liver and how effectively the liver can metabolize it, which the other options don’t capture.