A patient with severe hepatic cirrhosis is prescribed a drug that undergoes 95% first-pass hepatic extraction. How will cirrhosis most likely affect its oral bioavailability?

• A Bioavailability will decrease markedly because reduced hepatic blood flow slows drug absorption from the gut
• B Bioavailability will increase substantially because portosystemic shunting bypasses the liver, reducing first-pass extraction, and hepatocyte loss reduces intrinsic clearance ✓
• C Bioavailability will remain unchanged because the kidneys compensate for reduced hepatic clearance
• D Bioavailability will decrease because reduced albumin in cirrhosis increases unbound drug, accelerating renal elimination

Explanation

For high-extraction drugs (propranolol, lidocaine, morphine, labetalol), oral bioavailability is primarily determined by first-pass extraction. In cirrhosis, portosystemic collaterals (shunts) allow orally absorbed drug to bypass hepatic parenchyma entirely, and reduced functional hepatocyte mass further diminishes intrinsic clearance. Both effects markedly increase bioavailability, causing higher-than-expected plasma concentrations. Dose reduction is required for high-extraction drugs in cirrhotic patients.

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

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Written and medically reviewed by the StethoPrep medical team.