Sublingual and buccal routes bypass first-pass metabolism.

• A. False
• B. Not sure
• C. True
• D. Sometimes

Answer: (C)

The main idea here is how the route of administration affects exposure to hepatic first-pass metabolism. When a drug is absorbed through the sublingual or buccal mucosa, it enters the extensive network of capillaries under the tongue or inside the cheek and drains into the systemic circulation via veins that lead to the heart, bypassing the portal circulation that goes to the liver first. Because it avoids first-pass through the liver initially, most of the drug can reach systemic circulation intact, giving rapid onset and higher bioavailability for many medications such as nitroglycerin and other sublingual products.

There is a small caveat: if saliva is swallowed, some drug will enter the GI tract and be subject to first-pass metabolism. Despite that, the route itself is defined by bypassing the hepatic first-pass, making it true that sublingual and buccal administration largely bypass first-pass metabolism.