The total body clearance of propofol exceeds hepatic blood flow. What does this observation imply about its disposition?

• A Clearance measurement artefact from high plasma protein binding
• B Propofol undergoes substantial renal excretion of unchanged drug
• C Significant extrahepatic sites of metabolism exist, including lung and kidney ✓
• D Enterohepatic recirculation artificially inflates calculated clearance

Explanation

Since clearance cannot exceed organ blood flow if the liver were the sole eliminating organ, a measured clearance above hepatic blood flow proves extrahepatic metabolism. Evidence points to the lungs and kidneys contributing meaningfully. Clinically this matters because single-dose propofol kinetics are largely unchanged in cirrhosis, and clearance remains relatively preserved even in severe hepatic disease. Renal excretion of unchanged drug is negligible, and protein binding affects volume of distribution rather than creating this finding.

Reference: Miller's Anesthesia, 9th ed.

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