Propofol Pharmacokinetics — FRCA Primary MCQ
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Correct answer: C — Its total body clearance can exceed hepatic blood flow, indicating extrahepatic clearance
Explanation lettering: B = shown as A · D = shown as B · A = shown as D
C is correct. Propofol total body clearance can exceed hepatic blood flow, so hepatic metabolism alone cannot account for its elimination. Human organ-clearance studies demonstrate substantial extrahepatic metabolism, particularly by the kidneys; the lungs are not considered the principal extrahepatic site. Propofol is a weakly acidic phenol with a pKa of approximately 11, not 7.4. It is extensively metabolised to inactive glucuronide and sulphate conjugates, which are excreted in urine; negligible unchanged propofol is excreted renally. Commercial 1% and 2% preparations are oil-in-water lipid emulsions rather than solutions in Hartmann's solution. Pain on injection is very common with propofol and occurs more frequently than with thiopentone.
Reference: Hiraoka H, et al. Kidneys contribute to the extrahepatic clearance of propofol in humans, but not lungs and brain. British Journal of Clinical Pharmacology. 2005;60:176–182. https://pubmed.ncbi.nlm.nih.gov/16042671/