Not all oral drugs pass through the liver before reaching systemic circulation; some may bypass hepatic metabolism. Which statement is true?

• A. All oral drugs pass through the hepatic portal vein before systemic distribution.
• B. Some drugs can bypass the liver and reach systemic circulation via alternative routes.
• C. Oral drugs are never metabolized by the liver.
• D. First-pass metabolism always eliminates oral drugs completely.

Answer: (B)

The main idea is that the liver's first-pass metabolism can be bypassed by routes that deliver drug into systemic circulation without first draining through the hepatic portal vein. Normally, drugs absorbed from the gut enter the portal circulation and go to the liver, where a portion can be metabolized before reaching the rest of the body. But some routes avoid this path. For example, sublingual or buccal absorption lets drug enter the blood from the mouth directly into systemic circulation, bypassing the portal system and the first-pass effect. Other routes like transdermal, inhalation, or certain rectal routes can also reach systemic circulation without being exposed to the liver first. That’s why the statement that some drugs can bypass the liver and reach systemic circulation via alternative routes is true.

In contrast, all oral drugs do not necessarily pass through the portal vein (that bypass is possible with sublingual or other routes), oral drugs are not never metabolized by the liver (first-pass metabolism is a real factor for many), and first-pass metabolism does not always eliminate a drug completely—bioavailability can still be substantial for drugs with partial or minimal first-pass effect.