A drug undergoes extensive first-pass metabolism in the liver. If hepatic extraction ratio (EH) = 0.90, what is the approximate oral bioavailability?

• A 10% ✓
• B 90%
• C 45%
• D 50%

Explanation

Oral bioavailability (F) = 1 − EH, where EH is the hepatic extraction ratio (fraction extracted on first pass through the liver). With EH = 0.90, F = 1 − 0.90 = 0.10 = 10%. High-extraction drugs (EH >0.7) such as propranolol, morphine, lidocaine, and verapamil have very low oral bioavailability due to first-pass metabolism. For these drugs, hepatic blood flow (rather than intrinsic enzymatic capacity) is the rate-limiting determinant of clearance. Diseases that reduce hepatic blood flow (cirrhosis, heart failure) or drugs that alter hepatic perfusion can disproportionately increase plasma levels of high-extraction drugs.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.