Which of the following correctly describes the phenomenon of 'first-pass metabolism' and its clinical implication?

• A First-pass metabolism occurs in the plasma immediately after IV injection, before the drug reaches the target organ
• B First-pass metabolism refers to renal clearance occurring in the first hour after drug administration
• C First-pass metabolism only affects protein-bound drugs; free drugs pass through the liver unchanged
• D After oral ingestion, drugs absorbed from the small intestine pass through the portal circulation to the liver where significant hepatic metabolism can markedly reduce bioavailability before reaching systemic circulation ✓

Explanation

First-pass (presystemic) metabolism occurs when orally administered drugs, after absorption from the GI tract, enter the portal vein and pass through the liver before reaching systemic circulation. Hepatic enzymes (CYP450, MAO, conjugation enzymes) may extensively metabolise the drug, reducing bioavailability. Examples: propranolol (oral bioavailability ~30%), lignocaine (oral unusable, ~3% bioavailability), and glyceryl trinitrate (sublingual used to bypass). Drugs with high extraction ratios are most affected; sublingual, transdermal, or IV routes bypass first-pass metabolism.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.