In the well-stirred model, holding Clint and fu constant, what happens to CLh as hepatic blood flow Qh increases?

• A. CLh increases
• B. CLh decreases
• C. CLh remains unchanged
• D. CLh becomes zero

Answer: (A)

In the well-stirred liver model, hepatic clearance depends on both blood flow to the liver and the liver’s intrinsic ability to clear the drug. The relationship is given by CLh = Qh × (fu × Clint) / (Qh + fu × Clint). If Clint and fu are held constant, CLh changes with Qh in a saturating way. When Qh is small, CLh grows roughly in proportion to Qh. As Qh increases and becomes large compared to fu × Clint, CLh approaches fu × Clint and levels off. So increasing hepatic blood flow raises CLh, up to a maximum set by the intrinsic clearance.