Hepatic Extraction Ratio — FRCA Primary MCQ

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HardPharmacology - General PrinciplesHepatic Extraction RatioFRCA Primary

In a healthy adult receiving therapeutic drug concentrations, hepatic blood flow acutely decreases while plasma protein binding and hepatic intrinsic clearance remain unchanged. For which drug would hepatic clearance be expected to decrease most nearly in proportion to the reduction in hepatic blood flow?

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Correct answer: D — Propranolol

Propranolol is the correct answer. It undergoes extensive presystemic hepatic extraction and is a high-extraction drug; therefore, its hepatic clearance is predominantly flow-limited and falls substantially when hepatic blood flow decreases. Diazepam and warfarin are highly protein-bound, low-extraction drugs whose hepatic clearance is more sensitive to unbound fraction and intrinsic enzyme activity. Phenytoin is also capacity-limited and has saturable hepatic metabolism, producing concentration-dependent, nonlinear kinetics rather than flow-limited clearance. Digoxin is principally eliminated unchanged by the kidneys, so hepatic extraction contributes little to its total clearance. The original key was correct, but the explanation incorrectly grouped digoxin with hepatically cleared, protein-binding-dependent drugs.

Reference: Routledge PA, Shand DG. Clinical pharmacokinetics of propranolol. Clin Pharmacokinet. 1979;4:73–90. https://pubmed.ncbi.nlm.nih.gov/656285/