Propranolol has a hepatic extraction ratio above 0.7. After intravenous administration, which factor most directly determines its systemic clearance?

• A Rate of hepatic blood flow ✓
• B Intrinsic metabolic capacity of hepatocyte enzymes
• C Fraction of drug bound to plasma proteins
• D Fraction excreted unchanged by the kidney

Explanation

For high extraction ratio drugs the liver metabolizes essentially all drug presented to it, so clearance becomes limited by how fast blood delivers drug to the liver, a situation called flow-dependent clearance. Protein binding (option C) and intrinsic clearance (option B) matter mainly for low extraction drugs where clearance is capacity-limited. Clinically this is why propranolol clearance falls sharply in heart failure and cirrhosis, conditions that reduce hepatic perfusion.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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